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<title>bioRxiv Subject Collection: Cell Biology</title>
<link>https://biorxiv.org</link>
<description>
This feed contains articles for bioRxiv Subject Collection "Cell Biology"
</description>

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<title>bioRxiv</title>
<url>https://www.biorxiv.org/sites/default/files/bioRxiv_article.jpg</url>
<link>https://www.biorxiv.org</link>
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<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.25.734517v1?rss=1">
<title>
<![CDATA[
Basal BNIP3/NIX mitophagy is controlled by selective protection of sentinel receptors 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.25.734517v1?rss=1
</link>
<description><![CDATA[

                Mitochondrial homeostasis is maintained by multiple quality control pathways, including mitophagy, which targets dysfunctional mitochondria for degradation. During receptor-mediated mitophagy, the outer membrane proteins BNIP3 and NIX directly recruit autophagy machinery to the mitochondrial surface, though their precise regulation is still unclear. In recent years, new BNIP3- and NIX-interacting proteins have been identified that influence mitophagic flux. PPTC7 and FBXL4 target BNIP3 and NIX for proteasomal turnover to keep levels of the receptors low, whereas TMEM11 is proposed to spatially control mitophagy by interacting with receptors at active mitophagy sites. However, it is unclear how each of these interactions is controlled and how they interplay with each other. Here, we identify a repressor of mitophagy, ARMC1, which forms a complex with TMEM11, BNIP3, and NIX. During mitophagy activation, ARMC1 dissociates from the complex, freeing the receptors to initiate mitophagy. We find that TMEM11 then acts in an antagonistic relationship with PPTC7, protecting the receptors from proteasomal degradation. Our data are consistent with a two-stage model. At steady state, a population of sentinel receptors is repressed and primed to respond to mitochondrial dysfunction. Once mitophagy is activated, TMEM11 protects BNIP3 and NIX, ensuring a sustained mitophagic response. Our findings provide a framework for understanding how two key regulatory pathways intersect to modulate receptor-mediated mitophagy.
]]></description>
<dc:creator><![CDATA[ Kumar, A., Love, A., Kozul, K., Gok, M., Niemi, N., Friedman, J. ]]></dc:creator>
<dc:date>2026-6-26</dc:date>
<dc:identifier>doi:10.64898/2026.06.25.734517</dc:identifier>
<dc:title><![CDATA[Basal BNIP3/NIX mitophagy is controlled by selective protection of sentinel receptors]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-26</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.734689v1?rss=1">
<title>
<![CDATA[
Megalin deficiency perturbs retinal homeostasis and impairs cathepsin D processing and phagosome-lysosome maturation in the retinal pigment epithelium 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.734689v1?rss=1
</link>
<description><![CDATA[

                
                  The multiligand endocytic receptor, megalin (LRP2), is expressed in the retinal pigment epithelium (RPE) and patients lacking the receptor develop high myopia. Despite its established role in retinal development, the contribution of megalin to retinal homeostasis in the normally developed/mature eye remains poorly understood. Here, we investigated megalin function using an inducible knockout mouse (KO) model and human iPSC-derived RPE with megalin knockdown (KD) to distinguish post-developmental homeostatic functions from developmental effects.
                  In vivo, m
                  egalin ablation caused progressive retinal degeneration and visual impairment, with morphological abnormalities in the RPE but no changes in myopia-associated ocular phenotypes including axial length and intraocular pressure. Proteomic profiling of megalin-KO RPE revealed reduction of autophagy-related proteins. In line with this, megalin deficiency was associated with accumulation of pro-cathepsin D, and perturbed rhodopsin turnover. This was supported
                  in vitro
                  , where trafficking of photoreceptor outer segment (POS) containing phagosomes to lysosomes was reduced, suggesting disturbed phagosome maturation. Megalin KD did not measurably impair initial uptake of POS discs, but delayed rhodopsin degradation, indicating defective post-ingestion processing. Together, these findings establish megalin as a key regulator of retinal homeostasis in the mature eye by controlling phagosome-lysosome fusion in the RPE and suggest that megalin dysfunction contributes to slowly progressive retinal degeneration. This positions megalin as a potential therapeutic target in lysosomal degenerative diseases in the retina.
                
]]></description>
<dc:creator><![CDATA[ Rasmussen, D., Marschall, P., Lee, S., Storm, T., Jakobsen, T., Wu, Q., Askou, A., Fenton, R., Corydon, T., Mahajan, V., Nielsen, R. ]]></dc:creator>
<dc:date>2026-6-26</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.734689</dc:identifier>
<dc:title><![CDATA[Megalin deficiency perturbs retinal homeostasis and impairs cathepsin D processing and phagosome-lysosome maturation in the retinal pigment epithelium]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-26</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.25.734357v1?rss=1">
<title>
<![CDATA[
Design and Validation of a 3D-Printed Motorized Biaxial Cell Stretching Device 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.25.734357v1?rss=1
</link>
<description><![CDATA[

                Mechanical forces have a major effect on cell behavior. Most cells in vitro are grown under static conditions on hard tissue culture plastic, conditions that do not accurately reflect living tissues. The ability of cells to sense and respond to mechanical forces is essential for key biological processes, including development, proliferation, and migration. Disruption of the ability to respond to mechanical forces are known to be a critical factor in many diseases, including cardiovascular disease, progeria, and cancer. Here, we present the design, fabrication, and biological testing of a custom-built cell-stretching device that applies controlled biaxial strain to cells cultured on a polydimethylsiloxane (PDMS) membrane. We then used this device to examine how cells respond to strain. In response to biaxial strain, MCF-7 cells activated the mechanosensitive immediate early gene (IEX-1), with its expression increasing significantly after 1 and 3 hours of stretching. Cells exposed to mechanical strain also remodeled their cytoskeleton in a direction-dependent manner. Under uniaxial strain, actin filaments reoriented perpendicular to the stretch direction, whereas biaxially stretched cells do not promote directional reorientation, but instead appear to reinforce actin at the cell periphery. Similarly, cells under uniaxial strain exhibited changes in nuclear orientation and shape that were not observed under biaxial strain. Nuclear area remained unchanged in either strain condition. These results highlight that the biaxial stretcher can be used to apply strain to cells, and that cells respond differently to biaxial strain compared to what has been reported for uniaxial strain.
]]></description>
<dc:creator><![CDATA[ Kafour, N., Al-Maslamani, N., Al-Sammak, B., Horn, H. ]]></dc:creator>
<dc:date>2026-6-26</dc:date>
<dc:identifier>doi:10.64898/2026.06.25.734357</dc:identifier>
<dc:title><![CDATA[Design and Validation of a 3D-Printed Motorized Biaxial Cell Stretching Device]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-26</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.25.734520v1?rss=1">
<title>
<![CDATA[
Artificial endoplasmic reticulum-lipid droplet tethers facilitate lipid incorporation into lipid droplets 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.25.734520v1?rss=1
</link>
<description><![CDATA[

                Lipid droplets (LDs) are ubiquitous organelles that store neutral lipids to meet cellular energetic and signaling needs. As a unique monolayer structure, LDs arise from the endoplasmic reticulum (ER) and acquire proteins and lipids through their membrane contact sites (MCSs) with the ER. In this study, we exogenously induce ER-LD MCSs using a dimerization-dependent fluorescent protein (ddFP) system. Strikingly, inducing these MCSs increases LD size without influencing LD total amount per cell, in a manner that is distinct from LD biogenesis induced by the dietary fatty acid oleic acid. By examining the trafficking of the triacylglycerol synthesis enzyme DGAT2 under ddFP induction, we found that artificial tethering recruits LD proteins to the ER-LD interface but not to the LD surface, unlike oleic acid supplementation. However, by supplementing ddFP-transfected cells with fluorescent fatty acids, we found that ddFP-positive LDs preferentially incorporate exogenous lipid, suggesting that inducing MCSs can facilitate ER-to-LD lipid transfer. These results demonstrate ddFPs as a tool for manipulating LD MCSs and elucidate the role of ER-LD MCSs following LD biogenesis to continue to promote LD growth.
]]></description>
<dc:creator><![CDATA[ Williams, V., Miner, G., Cohen, S. ]]></dc:creator>
<dc:date>2026-6-26</dc:date>
<dc:identifier>doi:10.64898/2026.06.25.734520</dc:identifier>
<dc:title><![CDATA[Artificial endoplasmic reticulum-lipid droplet tethers facilitate lipid incorporation into lipid droplets]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-26</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.24.734246v1?rss=1">
<title>
<![CDATA[
Differential Enhancer Activity and FOXF1 Levels Contribute to Higher Inflammatory Gene Expression of Fetal/Neonatal Versus Adult Fibroblasts in IR-induced Senescence 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.24.734246v1?rss=1
</link>
<description><![CDATA[

                Some key inflammatory genes controlled by the RELA transcription factor are thought to be highly expressed in fibroblasts induced into senescence by ionizing radiation (IR) as part of the Senescent-Associated Secretory Phenotype (SASP). However, this view is based largely on studies of a limited number of fibroblast cell lines derived from fetal lung or neonatal foreskin. Here, we show that more than half of the primary adult fibroblast strains examined exhibit only weak induction of RELA-dependent inflammatory genes following IR-induced senescence. We define these fibroblasts as “low-responding” to distinguish them from fibroblasts that express high levels of inflammatory gene expression in response to IR. RNA-seq analysis indicated particularly weak IL1A and IL1B expression in low-responding fibroblasts. IL1-alpha and IL1-beta participate in a positive amplification loop for inflammatory gene expression in senescence. Addition of recombinant IL1-alpha or IL1-beta to these fibroblasts sufficed to induce high expression of inflammatory genes. Low-responding fibroblasts thus exhibit cell-autonomous defects in IL1A and IL1B gene activation in response to IR that explains their overall low expression of RELA-targeted inflammatory genes. This defect was correlated with reduced chromatin accessibility and H3-K27-acetylation at 2 putative enhancers in the intergenic region separating IL1A and IL1B, and deletion of either of these enhancers inhibited inflammatory gene expression in IR-induced senescence. Fibroblasts express distinct transcriptomes and we found that differential expression of the FOXF1 transcription factor gene in high-responding WI38 fetal lung fibroblasts contributes to inflammatory gene expression after IR. Our observations indicate that fibroblasts can be distinguished by their ability to manifest cell-autonomous induction of inflammatory genes under conditions of IR-induced senescence.
]]></description>
<dc:creator><![CDATA[ Hamed, R., Courbeyrette, R., Foote, A., Thibeault, S., Fortunel, N., Crabbe, L., MANN, C. ]]></dc:creator>
<dc:date>2026-6-25</dc:date>
<dc:identifier>doi:10.64898/2026.06.24.734246</dc:identifier>
<dc:title><![CDATA[Differential Enhancer Activity and FOXF1 Levels Contribute to Higher Inflammatory Gene Expression of Fetal/Neonatal Versus Adult Fibroblasts in IR-induced Senescence]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.23.733888v1?rss=1">
<title>
<![CDATA[
The Role of Fibrinogen-Mediated Platelet Aggregation in Subsequent Platelet-Driven Blood Clot Contraction 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.23.733888v1?rss=1
</link>
<description><![CDATA[

                
                  Background
                  Blood clot contraction/retraction depends on the force-generating actomyosin and on the platelet integrin αIIbβ3, which transmits intracellular forces to fibrin. Before clotting, fibrinogen binds to activated integrin αIIbβ3, mediating platelet aggregation. The relationship between platelet aggregation and subsequent platelet-driven clot contraction remains unclear.
                
                
                  Methods
                  We investigated the effects of platelet aggregation on clot contraction by selectively blocking the αIIbβ3-fibrinogen binding using the RGDW peptide. The ability of RGDW to disrupt αIIbβ3-fibrinogen binding was assessed by platelet aggregometry. The time-course of clot contraction was monitored optically in whole blood or platelet-rich plasma and modeled mathematically. Clot stiffness was assessed using Thromboelastography. The effect of the RGDW peptide on the structure of PRP-clots was examined using scanning electron microscopy.
                
                
                  Results
                  The RGDW peptide dose-dependently inhibited TRAP-induced platelet aggregation. Both in whole blood and in plasma, the peptide dose-dependently prolonged the lag-period and slowed the rate without affecting the final extent of contraction. Thromboelastography showed that RGDW dose-dependently increased maximum clot stiffness in blood. Scanning electron microscopy revealed that RGDW treatment resulted in formation of smaller fibrin agglomerates surrounding non-aggregated platelets. A theoretical model allowed us to decipher mechanisms underlying the kinetic effects of RGDW.
                
                
                  Conclusion
                  Blocking the binding of integrin αIIbβ3 to fibrinogen and preventing platelet aggregation delays and slows subsequent clot contraction without affecting the final degree of shrinkage. These findings indicate a modulatory role of fibrinogen-mediated platelet aggregation in clot contraction and highlight the unforeseen effects of selective inhibitors of platelet aggregation on the contraction of blood clots and thrombi.
                
]]></description>
<dc:creator><![CDATA[ Khabirova, A., Khismatullin, R., Saliakhutdinova, S., Evtugina, N., Buitrago, L., Purohit, P., Litvinov, R., Weisel, J. ]]></dc:creator>
<dc:date>2026-6-25</dc:date>
<dc:identifier>doi:10.64898/2026.06.23.733888</dc:identifier>
<dc:title><![CDATA[The Role of Fibrinogen-Mediated Platelet Aggregation in Subsequent Platelet-Driven Blood Clot Contraction]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.23.734091v1?rss=1">
<title>
<![CDATA[
PIEZO1 upregulation in spinal cord astrocytes during MOG
                  35-55
                  -induced EAE correlates with ECM remodeling 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.23.734091v1?rss=1
</link>
<description><![CDATA[

                
                  Background
                  Extracellular matrix (ECM) remodeling is increasingly recognized as an important component of neuroinflammatory pathology in multiple sclerosis (MS), yet the mechanisms by which CNS cells sense and respond to alterations in their mechanical environment and the spatial across which mechanical changes can influence cellular behavior remain poorly understood. Piezo1 is a mechanosensitive ion channel that regulates cellular responses to mechanical stimuli and has recently emerged as a potential modulator of neuroinflammation.
                
                
                  Methods
                  
                    Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 wildtype mice using myelin oligodendrocyte glycoprotein (MOG):
                    35-55
                    . Immunohistochemical analyses were performed in spinal cord gray matter (GM), normal-appearing white matter (NAWM), and white matter lesion (LES) regions to assess ECM remodeling, total Piezo1 expression, and astrocyte-specific Piezo1 expression during acute and chronic EAE stages. Correlations with clinical EAE severity were determined. In parallel, mixed primary murine glial cultures were exposed to substrates of different stiffness and analyzed by transcriptomic profiling to investigate mechanobiological responses
                    in vitro
                    .
                  
                
                
                  Results
                  ECM-associated proteins, including glial fibrillary acidic protein (GFAP), fibronectin-1 and matrix metalloproteinase-3 (MMP3), were regionally upregulated during EAE, indicating widespread tissue remodeling beyond focal inflammatory lesions. Total Piezo1 expression was increased within lesions and transiently elevated in GM, whereas astrocyte-specific Piezo1 remained persistently upregulated during both acute and chronic EAE. Astrocytic Piezo1 expression correlated closely with ECM remodeling and clinical EAE severity, particularly in GM and NAWM. Notably, both total and astrocyte-specific Piezo1 showed stronger associations with clinical disability than classical inflammatory markers. Transcriptomic analysis revealed pronounced stiffness-dependent responses in glial cells, including alterations in extracellular matrix organization, cytokine signaling, cell adhesion, and proliferative pathways.
                
                
                  Conclusions
                  Our findings identify astrocytic Piezo1 as a prominent component of neuroinflammatory tissue remodeling during EAE. The close association of Piezo1 with ECM alterations, clinical disease severity, and stiffness-dependent glial responses supports a link between neuroinflammation and mechanosensory signaling. These results highlight mechanosensation as a potentially important contributor to CNS pathology and establish Piezo1 alteration as a candidate biomarker for neuroinflammatory disease.
                
]]></description>
<dc:creator><![CDATA[ Hintze, M., Chunder, R., Schwarz, M., Nurmatov, Z., Lorke, M., Baecker, J., Holzbauer, K., Brockmann, E., Ekici, A., Boccaccini, A., Kuerten, S. ]]></dc:creator>
<dc:date>2026-6-25</dc:date>
<dc:identifier>doi:10.64898/2026.06.23.734091</dc:identifier>
<dc:title><![CDATA[PIEZO1 upregulation in spinal cord astrocytes during MOG
                  35-55
                  -induced EAE correlates with ECM remodeling]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.25.734433v1?rss=1">
<title>
<![CDATA[
Virus-mediated tau aggregate seeding in a cellular model 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.25.734433v1?rss=1
</link>
<description><![CDATA[

                Formation of neuronal tau protein aggregates is a defining feature of tauopathies, including Alzheimer’s disease and frontotemporal dementia. Tau pathology propagates across brain regions by a cell-to-cell aggregate seeding mechanism. While epidemiological and experimental studies over the past three decades have implicated viral infections in aggregate-associated neurodegeneration, the underlying mechanisms remain unclear. Here, we show in a cell culture model that seeding competent tau aggregates are efficiently packaged into lentiviral particles and induce tau aggregation in recipient cells in a virus receptor-dependent manner. Tau aggregates interact with the viral Gag polyprotein, likely facilitating their incorporation into virions. Virus-dependent tau seeding requires protease-mediated maturation of the envelope protein to enable efficient fusion of the viral envelope with the plasma membrane of the recipient cell. Thus, tau aggregate packaging is compatible with the formation of mature, infectious virions. These findings are consistent with a possible role of viral infection in neurodegenerative disease progression and offer a robust, versatile platform to model tau propagation in cellular systems and animal models.
]]></description>
<dc:creator><![CDATA[ Yuste-Checa, P., Martinez-Piera, R., Herrmann-Sim, F., Ronquillo-Silva, L., Korner, R., Hartl, F. ]]></dc:creator>
<dc:date>2026-6-25</dc:date>
<dc:identifier>doi:10.64898/2026.06.25.734433</dc:identifier>
<dc:title><![CDATA[Virus-mediated tau aggregate seeding in a cellular model]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.24.732965v1?rss=1">
<title>
<![CDATA[
TP53-mediated bidirectional lineage plasticity drives alveolar epithelial cell extrusion and tissue remodeling 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.24.732965v1?rss=1
</link>
<description><![CDATA[

                Cell extrusion contributes to epithelial homeostasis, but its dysregulation can lead to tumorigenesis or degeneration. A fine balance in this process is therefore essential for tissue integrity. Yet the cell types and states vulnerable to extrusion, and the mechanisms that drive it, remain elusive. Here, using spatial maps of cell states in human idiopathic pulmonary fibrosis (IPF) we find that aberrant TP53 activation in alveolar epithelial cells drives cell extrusion. Genetic modulation of TP53 specifically in alveolar epithelial type 1 cells (AT1) was sufficient to induce plasticity and subsequent extrusion as demonstrated by lineage tracing and live imaging. Strikingly, single cell and bulk transcriptome profiling revealed aberrant TP53 drives AT1 cells to acquire a transitional state mirroring AT2-derived regeneration associated intermediate states. Critically, loss of AT1 derived transitional state triggers a compensatory AT2-derived regenerative response, establishing a bidirectional transitional state that activates myofibroblasts and remodels the alveolus. Together, our study implicates AT1 plasticity and their reversion as an unrecognized driver of epithelial cell loss and establishes bidirectional transitional state as a central mechanism underlying progression of fibrotic remodeling.
]]></description>
<dc:creator><![CDATA[ Morowitz, J., Whitlow, T., Miyashita, N., Enkhbayar, K., Pratapa, A., Singh, R., Tata, A., Tata, P. ]]></dc:creator>
<dc:date>2026-6-25</dc:date>
<dc:identifier>doi:10.64898/2026.06.24.732965</dc:identifier>
<dc:title><![CDATA[TP53-mediated bidirectional lineage plasticity drives alveolar epithelial cell extrusion and tissue remodeling]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.23.733767v1?rss=1">
<title>
<![CDATA[
ATAD3A structurally links mtDNA replication and mitochondrial fission 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.23.733767v1?rss=1
</link>
<description><![CDATA[
Mitochondrial function depends on the maintenance of its genome, and disruptions in copy number and distribution are hallmarks of mitochondrial disorders. Mitochondrial DNA (mtDNA) replication is spatially and temporally linked to mitochondrial division (i.e., fission). However, the signal that coordinates these two events, which are physically separated by the barrier of two mitochondrial membranes, remains unknown. To gain insight into this coordination, we employed correlative cryo-electron tomography (cryo-ET) to analyze the microenvironment surrounding replicating nucleoids. Mitochondrial regions containing replicating mtDNA exhibit a unique membrane architecture defined by the presence of clustered, membrane-spanning tethers that traverse the inner membrane space. Using a combination of superresolution microscopy and genetically encoded cryo-ET tagging technology, we identify these tethers as the AAA+ ATPase ATAD3A. We further show that ATAD3A knockdown reduces recruitment of the mitochondrial fission machinery, whereas overexpression promotes its recruitment and subsequent fission. Our work suggests that ATAD3A forms nanoscale linkages that coordinate these two distinct processes, revealing a new structural paradigm for organellar communication across distinct membrane-defined environments.
                
                  Highlights
                  
                    
                      Replicating mitochondrial DNA (mtDNA) nucleoids are surrounded by a distinct membrane microenvironment.
                    
                    
                      ATAD3A forms membrane-spanning tethers enriched at replicating mtDNA sites.
                    
                    
                      ATAD3A enrichment is necessary and sufficient to recruit mitochondrial fission machinery and induce fission at mtDNA replication sites.
                    
                    
                      ATAD3A structurally couples mtDNA replication state to mitochondrial fission across distinct organellar subcompartments.
                    
                  
                
]]></description>
<dc:creator><![CDATA[ Dua, N., Ma, B., Oviedo, S., Rahmani, H., Boyd, T., Park, D., Wiseman, L., Grotjahn, D. ]]></dc:creator>
<dc:date>2026-6-25</dc:date>
<dc:identifier>doi:10.64898/2026.06.23.733767</dc:identifier>
<dc:title><![CDATA[ATAD3A structurally links mtDNA replication and mitochondrial fission]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.24.734384v1?rss=1">
<title>
<![CDATA[
CWF19L2 couples pre-mRNA alternative splicing with the maternal-to-zygotic transition to safeguard female fertility 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.24.734384v1?rss=1
</link>
<description><![CDATA[

                
                  The maternal-to-zygotic transition (MZT) requires precise spatiotemporal execution of pre-mRNA alternative splicing (AS), yet the core splicing machinery driving this developmental reprogramming remains incompletely understood. Here, we identify the CWF19-like protein 2 (CWF19L2) as an indispensable pre-mRNA AS regulator that safeguards against oocyte and early embryo competence defects (OECD). While murine germline-specific depletion of
                  Cwf19l2
                  spares morphological folliculogenesis, oocyte maturation, or fertilization, it induces complete female sterility characterized by profound developmental arrest at the 2-cell stage. Mechanistically, maternal deficiency of CWF19L2 localized to nuclear speckles disrupts transcription-splicing-translation coupling, collapsing AS homeostasis during maternal reserves and zygotic genome activation. We further demonstrate that CWF19L2 orchestrates the pre-mRNA splicing network through directly binding to target transcripts and indirectly modulating via interacting with the core spliceosomal factor PRPF8. Importantly, exogenous
                  Cwf19l2
                  mRNA partially rescues the embryonic arrest. Together, our findings establish CWF19L2 as an indispensable AS engine during the MZT, providing a mechanistic foundation for OECD and a novel molecular etiology for female infertility.
                
]]></description>
<dc:creator><![CDATA[ Wang, S., Li, T., Cai, Y., Shangguan, K., Wang, Z., Huang, C., Shi, Y., Xin, J., Zhao, Q., Zhang, H., Zhao, H., Guo, Y., Liu, H., Chen, Z., Huang, T. ]]></dc:creator>
<dc:date>2026-6-25</dc:date>
<dc:identifier>doi:10.64898/2026.06.24.734384</dc:identifier>
<dc:title><![CDATA[CWF19L2 couples pre-mRNA alternative splicing with the maternal-to-zygotic transition to safeguard female fertility]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.22.733743v1?rss=1">
<title>
<![CDATA[
Rho1 and Rgf3 regulate the expansion of the nuclear envelope during fission yeast mitosis/cytokinesis 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.22.733743v1?rss=1
</link>
<description><![CDATA[

                
                  The nuclear envelope (NE) surrounds the genetic material and is continuous with the endoplasmic reticulum (ER). In yeast and other organisms undergoing closed mitosis, nuclear envelope expansion (NME) is strictly required to accommodate spindle elongation and ensure proper chromosome segregation within a single nuclear compartment. Failure to expand the NE during mitosis leads to chromosome missegregation. Here, we show that deletion of the unstructured N-terminal domain of Rgf3, a Rho1-specific guanine nucleotide exchange factor (GEF), causes early mitotic defects that produce the characteristic “cut” phenotype of untimely cell division. The
                  rgf3
                  ΔN2 mutant displays spindle buckling, a hallmark of anaphase nuclei unable to properly expand the NE. From yeast to mammals, phosphatidic acid (PA)—a key precursor in phospholipid biosynthesis—is metabolized via two competing pathways, the cytidine diphosphate–diacylglycerol (CDP–DAG) and the Kennedy pathways, both contributing to lipid membrane homeostasis. We provide evidence that impaired Rho1 activation in
                  rgf3
                  ΔN2 selectively disrupts phospholipid synthesis through the CDP-choline branch of the Kennedy pathway. Thus, Rho1 promotes mitotic progression by modulating phospholipid biosynthesis to enable efficient NME during anaphase.
                
                
                  Highlights
                  The N-terminus of Rgf3 is required for proper nuclear envelope expansion (NME) during anaphase.
                  The structurally flexible N-terminal domain of Rgf3 is essential for localized Rho1 activation.
                  Active Rho1 drives mitotic membrane growth by modulating phospholipid synthesis through the Kennedy pathway.
                
]]></description>
<dc:creator><![CDATA[ Celador, R., Garcia, P., Tajadura, V., Edreira, T., Casasampere, M., Moseley, J., Sanchez, Y. ]]></dc:creator>
<dc:date>2026-6-25</dc:date>
<dc:identifier>doi:10.64898/2026.06.22.733743</dc:identifier>
<dc:title><![CDATA[Rho1 and Rgf3 regulate the expansion of the nuclear envelope during fission yeast mitosis/cytokinesis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.24.734187v1?rss=1">
<title>
<![CDATA[
SETDB1 promotes tubulin deacetylation and Golgi fragmentation by HDAC6 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.24.734187v1?rss=1
</link>
<description><![CDATA[

                Microtubules (MTs) are dynamic cytoskeletal structures essential for intracellular transport, cell division, and organelle positioning. Their functions are regulated by post-translational modifications, including α-tubulin acetylation at Lys40, which enhances MT stability and resilience. Histone deacetylase 6 (HDAC6) is the primary enzyme that reverses this modification, but its access to the luminal Lys40 residue is restricted. Previously, we identified SETDB1, a histone methyltransferase and known oncogene, as a cytoplasmic regulator of MT dynamics, attenuating MT polymerization and destabilizing MTs. Here, we uncover the molecular mechanism by which SETDB1 destabilizes MTs. SETDB1 interacts with HDAC6 and promotes its tubulin deacetylation activity. Mechanistically, SETDB1 enhances HDAC6 recruitment to polymerized MTs and induces repairable damage along MT shafts, generating entry points for HDAC6 into the MT lumen. Functionally, this axis regulates Golgi organization: SETDB1 overexpression disperses the Golgi in an HDAC6-dependent manner, while SETDB1 knockdown or HDAC6 inhibition compacts it. Notably, SETDB1’s role in Golgi regulation is independent of its methyltransferase activity. These findings reveal crosstalk among the histone methylation machinery, MT dynamics, and Golgi organization. Since Golgi dispersal is thought to promote tumorigenesis, our results suggest that the SETDB1-HDAC6 axis is a potential therapeutic target.
                
                  Graphical 
                  
                    
                  
                
]]></description>
<dc:creator><![CDATA[ Gunasekaran, G., Gelman, G., Manshirov, O., Listovsky, T., Gerlitz, G. ]]></dc:creator>
<dc:date>2026-6-25</dc:date>
<dc:identifier>doi:10.64898/2026.06.24.734187</dc:identifier>
<dc:title><![CDATA[SETDB1 promotes tubulin deacetylation and Golgi fragmentation by HDAC6]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.20.733546v1?rss=1">
<title>
<![CDATA[
Cofilin controls actin network identity by sorting actin binding proteins to distinct cytoskeletal structures 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.20.733546v1?rss=1
</link>
<description><![CDATA[

                Proper cell physiology requires the co-assembly of multiple actin cytoskeletal networks that are tailored for specific functions. To maintain and promote the different functions of these networks, cells decorate them with distinct types of actin binding proteins (ABPs). While various models have been proposed to explain this selective sorting of ABPs, the role of actin disassembly factors is less well understood. Here, we used inducible CRISPR interference and quantitative live-cell imaging to test how disassembly factors control the ABP composition of different networks. We found that knockdown of cofilin (Cof1), a potent and highly conserved disassembly factor, disrupts the size, organization, and ABP composition of actin networks. Specifically, defects in Cof1-mediated disassembly disrupt intracellular transport due to the assembly of overgrown and disordered branched actin networks that are inappropriately decorated by tropomyosin (Tpm1). Contrary to prevailing models of ABP sorting, these networks are co-decorated by Tpm1 and fimbrin (Sac6), and their assembly is independent of formin activity. Instead, our findings support a model wherein failure to maintain the proper architecture of branched actin networks drives mis-localization of network-specific ABPs. Together, this work demonstrates that actin disassembly factors play a critical role in maintaining cytoskeletal structure and function to regulate ABP sorting across distinct networks.
]]></description>
<dc:creator><![CDATA[ Radcliffe-Hines, D., Santiago, R., Reading, A., Hercyk, B., Evans, C., McInally, S. ]]></dc:creator>
<dc:date>2026-6-25</dc:date>
<dc:identifier>doi:10.64898/2026.06.20.733546</dc:identifier>
<dc:title><![CDATA[Cofilin controls actin network identity by sorting actin binding proteins to distinct cytoskeletal structures]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.24.734396v1?rss=1">
<title>
<![CDATA[
Myeloid Suclg2 deficiency attenuates aortic dissection by reshaping succinate-associated macrophage remodelling 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.24.734396v1?rss=1
</link>
<description><![CDATA[

                
                  Background
                  Succinate has emerged as an immunometabolic mediator of cardiovascular diseases. However, the enzymatic mechanisms linking macrophage succinate metabolism to aortic dissection remain incompletely understood. This study investigated whether Suclg2, which encodes the GDP-forming β-subunit of succinyl-CoA ligase, regulates succinate-associated macrophage remodelling and aortic dissection progression.
                
                
                  Methods
                  Suclg2 expression was examined in BAPN-induced AD and human acute type A aortic dissection tissues by Western Blot and immunofluorescence. Myeloid- and smooth muscle cell-specific Suclg2 conditional knockout mice were subjected to BAPN treatment to evaluate survival, aortic outcomes, histological injury and aortic morphology. Aortic RNA-seq was used to discover transcriptional changes. Bone marrow-derived macrophages were analysed under basal, M1-like and M2-like conditions to assess macrophage-intrinsic transcriptional responses. Plasma succinate levels and untargeted metabolomic profiles were further examined.
                
                
                  Results
                  Suclg2 was increased in murine and human dissected aortas and partially localized to CD68⁺ cells. Myeloid Suclg2 deletion markedly reduced BAPN-induced aortic rupture and dissection, whereas smooth muscle cell Suclg2 deletion did not confer comparable protection. Aortic transcriptomic analysis showed that myeloid Suclg2 deficiency attenuated inflammatory adhesion and matrix-destructive programmes. In macrophages, Suclg2 deletion did not induce a simple M1/M2 polarization shift; instead, it remodelled lipid-handling, phagolysosomal, adhesive and matrix-remodelling pathways across stimulation states. Metabolic profiling showed reduced circulating succinate and broader changes in central carbon, lipid-associated, nucleotide and redox-related metabolites after myeloid Suclg2 deletion.
                
                
                  Conclusions
                  Myeloid Suclg2 is a succinate-associated immunometabolic regulator of aortic dissection. Its deficiency protects against aortic dissection by reshaping macrophage inflammatory-remodelling programmes and the systemic metabolic environment.
                
]]></description>
<dc:creator><![CDATA[ Xie, M., Gao, S., Xie, E., Gao, H., Zhang, K., Shen, Z., Sun, X. ]]></dc:creator>
<dc:date>2026-6-25</dc:date>
<dc:identifier>doi:10.64898/2026.06.24.734396</dc:identifier>
<dc:title><![CDATA[Myeloid Suclg2 deficiency attenuates aortic dissection by reshaping succinate-associated macrophage remodelling]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.24.734151v1?rss=1">
<title>
<![CDATA[
Germline mitophagy selectively eliminates deleterious mitochondrial DNA across generations 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.24.734151v1?rss=1
</link>
<description><![CDATA[

                
                  Faithful transmission of genetic information through the immortal germline is essential for organismal health and species survival, yet how mutant mitochondrial genomes (mtDNAs) are selectively eliminated across generations remains unclear. Here, we show that germline mitophagy functions as a mutation-responsive surveillance system that selectively eliminates mutant mtDNAs and shapes inheritance across generations. In
                  C. elegans
                  , mitochondria enriched for mutant mtDNAs are selectively removed in the maternal germline prior to oocyte fertilization via PINK1/Parkin-dependent and BNIP3-mediated mitophagy pathways activated by mtDNA defects. Germline mitophagy declines with age, resulting in offspring that inherit increased burdens of mutant mtDNAs. Conversely, enhancing mitophagy within germ cells restricts the transmission of deleterious genomes in a compounding manner, ultimately driving their complete elimination from the matrilineal lineage. Together, our findings demonstrate that germline mitophagy is a critical determinant of intergenerational mitochondrial genome inheritance, establishing its role in restricting the transmission of defective genetic information.
                
]]></description>
<dc:creator><![CDATA[ Ahier, A., Onraet, T., Campbell, D., Townsend, B., Geleta, A., Dowlath, S., Hahn, A., Lee, R., Dai, C., Gaudin, A., Pagan, J., Zuryn, S. ]]></dc:creator>
<dc:date>2026-6-25</dc:date>
<dc:identifier>doi:10.64898/2026.06.24.734151</dc:identifier>
<dc:title><![CDATA[Germline mitophagy selectively eliminates deleterious mitochondrial DNA across generations]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.23.733833v1?rss=1">
<title>
<![CDATA[
Volumetric Flow Imaging Microscopy to Enhance Particle Characterization 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.23.733833v1?rss=1
</link>
<description><![CDATA[

                
                  Flow imaging microscopy (FIM) is an important technology for high-throughput characterization of microscopic particles and microorganisms. However, conventional FIM relies on single-plane imaging (SPI), resulting in out-of-focus particles, reduced measurement precision, and incomplete characterization of irregularly shaped objects extending along the z-axis. To address these limitations, a volumetric flow imaging (VFI) framework was developed and implemented on the portable ARTiMiS platform. This approach captures multiple frames along the z-axis and extracts the highest fidelity image for each particle, which can also be used for single image generation with all particles in focus (i.e., all in focus image) and for three-dimensional reconstruction of irregularly shaped objects. Benchmarking VFI with microspheres, live cells (
                  Chlorella vulgaris
                  ), and filamentous cyanobacteria demonstrated increased fraction of particles in focus, reduced variability in particle size measurement, and increased resolvability of elongated particles in comparison to conventional SPI on commercially available FIM technologies. For
                  C. vulgaris
                  , VFI-derived size distributions closely matched curated FlowCam measurements without requiring post-processing to exclude out-of-focus particles. All-in-focus image reconstruction enabled simultaneous visualization of particles distributed across multiple depths and consistently resolved a greater proportion of filamentous structures as compared to SPI. For
                  Aphanizomenon
                  sp.,
                  Dolichospermum
                  sp., and
                  Planktothrix agardhii
                  , the SPI approach captured only 84%, 61%, and 58%, respectively, of the total filament length resolved by AIF reconstruction. Beyond image-based characterization, VFI enabled estimation of dynamic particle properties such as sinking velocity and mass density. Application of this framework to
                  C. vulgaris
                  cultures revealed distinct mass-density trajectories under nitrogen-replete and nitrogen-deplete conditions, with cell mass density increasing over time under nitrogen-replete conditions and decreasing under nitrogen deprivation. Collectively, these results establish VFI as a next-generation framework for FIM that expands its analytical capabilities beyond conventional morphometric characterization and provides new opportunities for single-cell-enabled environmental monitoring and biomanufacturing.
                
]]></description>
<dc:creator><![CDATA[ Khan, F., Gincley, B., Khan, F., Pinto, A. ]]></dc:creator>
<dc:date>2026-6-25</dc:date>
<dc:identifier>doi:10.64898/2026.06.23.733833</dc:identifier>
<dc:title><![CDATA[Volumetric Flow Imaging Microscopy to Enhance Particle Characterization]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.23.733857v1?rss=1">
<title>
<![CDATA[
Tubulin autoregulation mediator TTC5 regulates neuronal morphology and migration 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.23.733857v1?rss=1
</link>
<description><![CDATA[
Summary
                
                  Microtubule dynamics regulation is critical for neuronal development, yet how neurons regulate tubulin levels remains poorly understood. Tetratricopeptide repeat domain 5 (TTC5) mediates the co-translational degradation of tubulin transcripts in response to excess soluble tubulin, a.k.a. “tubulin autoregulation”, and TTC5 mutations are associated with cerebral atrophy, speech and motor impairment. Despite clinical relevance, the role of TTC5 and tubulin autoregulation in neurons has not been established. Using human induced pluripotent stem cells (iPSCs)-derived cortical-like neurons, we demonstrate that tubulin autoregulation is active in neurons and fully TTC5-dependent. Loss of TTC5 function suppresses microtubule polymerization and impairs axonal outgrowth and arborization, while enhancing cellular motility. These phenotypes recapitulate
                  in vivo
                  where TTC5 loss in mouse cerebral cortex projection neurons disrupts axon and dendrite arborization and drives aberrant hypermigration. Patient disease mutants phenocopy this motility dysregulation, directly linking TTC5 dysfunction to clinically relevant neurological deficits. Together, our findings establish tubulin autoregulation and its mediators as essential regulators of neuronal morphogenesis and connectivity and provides a mechanistic framework for understanding TTC5-associated neurodevelopmental disease.
                
]]></description>
<dc:creator><![CDATA[ Sarbanes, S., Ziak, J., Kolodkin, A., Roll-Mecak, A. ]]></dc:creator>
<dc:date>2026-6-24</dc:date>
<dc:identifier>doi:10.64898/2026.06.23.733857</dc:identifier>
<dc:title><![CDATA[Tubulin autoregulation mediator TTC5 regulates neuronal morphology and migration]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.23.733964v1?rss=1">
<title>
<![CDATA[
Acetylation-dependent remodeling of the secretory pathway shapes the senescence-associated secretome 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.23.733964v1?rss=1
</link>
<description><![CDATA[

                Cellular senescence is characterized by stable cell cycle arrest and the senescence-associated secretory phenotype (SASP), which drives tissue remodeling and inflammation. Underlying SASP with its increased secretion of cytokines and other secreted proteins is a massive reorganization of the secretory pathway. While transcriptional regulation of senescence has been extensively studied, the contribution of post-translational modifications (PTM) to secretory pathway regulation remains poorly understood.
                Here, we combined quantitative proteomics with multi-layered PTM profiling of phosphorylation, ubiquitination and acetylation to investigate how intracellular trafficking and secretion are regulated in senescence. Using doxorubicin-induced senescence as the primary model, we identified extensive proteome remodeling, with pronounced changes in ER–Golgi-associated pathways and secretory machinery. Acetylation emerged as the most prominently regulated PTM, particularly affecting proteins involved in vesicle trafficking and ER proteostasis. Comparable proteome and PTM remodeling were also observed in replicative senescence, indicating that these changes are not restricted to a single senescence model.
                Functional analyses revealed activation signatures of the acetyltransferases p300/CBP, linking global acetylation changes to enzymatic activity. Pharmacological inhibition of p300/CBP using A485 selectively modulated senescence-associated features without reversing growth arrest, consistent with a senomorphic-like effect during senescence establishment. Secretome profiling further demonstrated changes in the composition of secreted factors, consistent with modulation of the senescence-associated secretory phenotype.
                Together, these findings indicate that acetylation-dependent regulation of the secretory pathway shapes the senescence-associated secretome, revealing a mechanistic link between post-translational regulation, intracellular trafficking, and extracellular signaling in senescence.
]]></description>
<dc:creator><![CDATA[ Nasrashvilli, T., Emini, B., Cirri, E., Rahnis, N., Poempner, N., Gerner, C., Grillari, J., Heller, R., Kaether, C. ]]></dc:creator>
<dc:date>2026-6-24</dc:date>
<dc:identifier>doi:10.64898/2026.06.23.733964</dc:identifier>
<dc:title><![CDATA[Acetylation-dependent remodeling of the secretory pathway shapes the senescence-associated secretome]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.23.733989v1?rss=1">
<title>
<![CDATA[
Dynamic regulation of the Bcl-xL-BAD interaction 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.23.733989v1?rss=1
</link>
<description><![CDATA[

                
                  Background
                  The interaction between the anti-apoptotic protein Bcl-xL and the BH3-only sensitizer BAD represents a critical regulatory checkpoint in the intrinsic apoptotic pathway. Although this interaction is known to influence mitochondrial fate, its dynamic regulation and structural determinants in living cells remain poorly understood. Here, we developed a fluorescence lifetime imaging microscopy-based Förster resonance energy transfer (FLIM-FRET) platform to visualize and quantify Bcl-xL-BAD interactions in real-time.
                
                
                  Methods
                  We developed a quantitative fluorescence lifetime-based FRET (FLIM-FRET) approach to visualize and measure Bcl-xL-BAD interactions in single living glioblastoma cells. Stable GFP/Venus-Bcl-xL and mCherry-BAD FRET pairs were created, followed by acceptor photobleaching FRET, FLIM-FRET, Annexin V-BFP-based apoptosis assays, pharmacological perturbation using BH3 mimetics, and molecular dynamics simulations with MM/GBSA analysis. Statistical significance was assessed using appropriate parametric tests across multiple independent experiments.
                
                
                  Results
                  Using this platform, we observed that apoptotic stress markedly enhances the engagement of Bcl-xL and BAD. Increased FRET efficiency coincided with Annexin V positivity and nuclear condensation, indicating that maximal BAD binding reflects a higher level of apoptotic commitment. Structure-function analysis using targeted Bcl-xL mutants revealed distinct binding requirements: disruption of the core hydrophobic groove (Y101K) abolished BAD binding and impaired BH3 mimetic sensitivity, whereas mutation within the BH1 domain (G138A) preserved BAD interaction and sensitivity to BH3 mimetics. Molecular dynamics simulations corroborated these observations by revealing preserved BAD-binding energetics in the G138A mutant, but destabilization in the Y101K mutant.
                
                
                  Conclusions
                  Together, these findings demonstrate the utility of a live-cell FLIM-FRET platform for resolving protein-protein interactions involving apoptotic proteins at the single-cell level. By linking interaction dynamics, structural determinants, and functional outcomes, this approach provides a broadly applicable framework for studying apoptotic priming, structural tolerance at BCL-2 family interfaces, and cellular responses to BH3-mimetic therapies.
                
]]></description>
<dc:creator><![CDATA[ Halikar, A., Rather, A., M, Z., K.C, S., TR, S. ]]></dc:creator>
<dc:date>2026-6-24</dc:date>
<dc:identifier>doi:10.64898/2026.06.23.733989</dc:identifier>
<dc:title><![CDATA[Dynamic regulation of the Bcl-xL-BAD interaction]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.23.733987v1?rss=1">
<title>
<![CDATA[
Developing High Content Imaging Functional Panels to Characterize Synovial Fibroblasts in Rheumatoid Arthritis 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.23.733987v1?rss=1
</link>
<description><![CDATA[

                
                  Objective
                  To develop and apply a preclinical functional imaging assay for visualizing and analyzing activated synovial fibroblasts (SFs) at single-cell resolution using high-content imaging.
                
                
                  Methods
                  A multiparametric functional imaging assay was developed to simultaneously interrogate six key cellular processes in cultured SFs from non-inflammatory control (NIC), osteoarthritis (OA) and rheumatoid arthritis (RA) patients. Two complementary fluorescent panels — comprising LipidTOX, MitoSOX, TMRM, EdU Click-iT, CYTO-ID, and Sir-Lysosome — collectively captured autophagy dynamics, mitochondrial health, lipid metabolism, and cellular proliferation within a single imaging workflow. Automated image acquisition and quantitative feature extraction via CellProfiler yielded approximately 1,200 morphological and intensity-based features per cell, enabling high-dimensional, unbiased phenotypic profiling at the individual cell level.
                
                
                  Results
                  Application of this assay revealed marked heterogeneity in basal cellular functions among SFs stratified by disease state, and robustly differentiated between NIC, OA and RA SFs. Stimulation with inflammatory cytokines (TNF-α, IL-1β, IFNƔ) and toll-like receptor ligands (LPS, poly I:C) elicited distinct, stimulus-dependent phenotypic responses across disease groups. Multiparametric analysis and feature importance ranking identified IL-1β as a key driver of enhanced autophagic activity, accompanied by significant remodeling of lipid metabolic profiles.
                
                
                  Conclusion
                  We developed a scalable, sensitive approach for dissecting functional heterogeneity in primary SF cultures, revealing previously unappreciated complexity in SF biology across disease states. Our approach provides a robust framework for high-throughput drug screening and identification of candidate therapeutics selectively targeting pathogenic fibroblast functions in inflammatory arthritis.
                
]]></description>
<dc:creator><![CDATA[ Laphanuwat, P., Ezen, E., Seiler, C., Ospelt, C. ]]></dc:creator>
<dc:date>2026-6-24</dc:date>
<dc:identifier>doi:10.64898/2026.06.23.733987</dc:identifier>
<dc:title><![CDATA[Developing High Content Imaging Functional Panels to Characterize Synovial Fibroblasts in Rheumatoid Arthritis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.23.734037v1?rss=1">
<title>
<![CDATA[
Fluid shear stress has a biphasic effect on clathrin-mediated endocytosis in vascular endothelial cells 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.23.734037v1?rss=1
</link>
<description><![CDATA[

                
                  Vascular endothelial cells (ECs) form a monolayer lining blood vessels and serve as a barrier between blood and tissues. Clathrin-mediated endocytosis (CME) is a major internalization pathway that involves a physical conformational change of the plasma membrane to form a vesicle and is therefore sensitive to the local environment. ECs are subjected to a myriad of fluid shear stress (FSS) rates from circulating blood, which we hypothesize affects CME. To test this, we used simultaneous two-wavelength axial ratiometry (STAR) microscopy, which provides nanoscale axial resolution, to determine the frequency and morphology of clathrin-coated vesicles as they form. Human umbilical vein endothelial cells (HUVECs) were transfected with dual-tagged clathrin light chain a (CLCa-iRFP-EGFP) and cultured under 10 dyn/cm
                  2
                  FSS. CME activity was elevated in cells cultured under flow and assayed in static or flow conditions compared to statically cultured and imaged controls, indicating that FSS-induced changes to CME were maintained shortly after flow cessation. Single vesicle analysis showed cells cultured in FSS had a slight preference for vesicle formation with a flat-to-curved clathrin transition compared to control. Next, to assess the impact of different FSS rates, we cultured HUVECs at 20 and 40 dyn/cm
                  2
                  FSS. We found total CME frequency was elevated compared to control at 20 dyn/cm
                  2
                  , but not 40 dyn/cm
                  2
                  . HUVECs cultured at both 20 and 40 dyn/cm
                  2
                  had vesicles with increased lifetime and enhanced stability, as well as a higher proportion of vesicles formed through a flat-to-curved transition of clathrin.
                
]]></description>
<dc:creator><![CDATA[ Yuan, J., Nawara, T., Seeley, L., Tran, Y., Mattheyses, A. ]]></dc:creator>
<dc:date>2026-6-24</dc:date>
<dc:identifier>doi:10.64898/2026.06.23.734037</dc:identifier>
<dc:title><![CDATA[Fluid shear stress has a biphasic effect on clathrin-mediated endocytosis in vascular endothelial cells]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.20.733393v1?rss=1">
<title>
<![CDATA[
Flow-Induced Yap/Taz Signaling Balances Endothelial and Hematopoietic Stem Cell Fates 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.20.733393v1?rss=1
</link>
<description><![CDATA[

                Mechanical forces from blood flow are essential for production of hematopoietic stem and progenitor cells (HSPCs) during embryogenesis, but the molecular mechanisms by which hemodynamic cues are sensed and orchestrate endothelial-to-hematopoietic (EHT) transition remain incompletely defined. We previously identified YAP mechanotransduction as a key integrator of physical forces with EHT. Here we show that hemodynamic forces can activate YAP signaling via the mechanoresponsive ion channel Piezo1 in human iPSC-derived hemogenic endothelium (HE) and zebrafish embryos. Investigation of the Piezo1/YAP axis revealed shared and unique roles of YAP and its paralogue TAZ in EHT. Mechanistically, we find a requirement for the Tead DNA-binding co-factor in YAP/TAZ-dependent control of HSPC number, and note that TAZ uniquely augments transcriptional output of the hematopoietic master regulator Runx1 via direct protein-protein interactions. By comprehensive scRNA-sequencing of YAP/TAZ gain-of-function (GOF) and yap-deficient cells from zebrafish, we reveal that YAP/TAZ promotes HSC production by positively regulating gene programs for hematopoietic self-renewal, cell cycle, and glycolysis-to-oxidative phosphorylation switching, while preventing reversion to endothelial identity. Importantly, comparison of GOF transcriptomes and functional analyses suggest decoupling of metabolic/proliferative and endothelial gene regulatory modules between YAP and TAZ: while either can functionally compensate for loss of the other in EHT, indiscriminate overactivation of TAZ enhances an endothelial program over pro-hematopoietic fate, ultimately blunting progression of HSPC production. Given that hemodynamic cues are integrated simultaneously by arterial and HE cells in embryonic vessels in which EHT occurs, these findings have strong implications for strategies designed to introduce biomechanical cues to in vitro hematopoietic differentiation systems to drive HSC production.
]]></description>
<dc:creator><![CDATA[ Sugden, W., George, S., LeBlanc, Z., Walcheck, M., Meader, E., Goldstein, J., Molnar, E., Zhu, W., Mout, R., Li, C., Radeke, L., Young, Z., Tillio, M., Falchetti, M., Najia, M., Tang, Y., Love, B., Jing, R., Tompkins, A., Stockard, O., Kubaczka, C., Kirchhof, K., Lundin, V., MacCrae, C., Schlaeger, T., Daley, G., North, T. ]]></dc:creator>
<dc:date>2026-6-23</dc:date>
<dc:identifier>doi:10.64898/2026.06.20.733393</dc:identifier>
<dc:title><![CDATA[Flow-Induced Yap/Taz Signaling Balances Endothelial and Hematopoietic Stem Cell Fates]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-23</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.22.733272v1?rss=1">
<title>
<![CDATA[
MOTS-c Coordinates Inter-Organellar Proteostasis for Adaptation to Chronic Metabolic Stress 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.22.733272v1?rss=1
</link>
<description><![CDATA[

                
                  Mitochondrial communication coordinates adaptive responses across organelles to sustain cellular homeostasis, a network that declines with age and contributes to loss of proteostasis. Here, we identify MOTS-c, an exercise-induced mitochondrial-derived peptide (MDP) encoded within the 12S rRNA locus, as an inter-organellar arm of the mitochondrial stress response (MSR) that links mitochondrial signaling to endoplasmic reticulum (ER) proteostasis and enables adaptation to chronic stress. Using progressive stress media (PSM), a model of gradual and multifactorial metabolic stress, we show that MOTS-c enables adaptation through a biphasic program: acutely, a reversible, ATF4-independent suppression of protein synthesis; and chronically, an ATF6-biased ER unfolded protein response (UPR
                  ER
                  ) with tempered ATF4 engagement and coordinated metabolic remodeling. Whereas mitochondrial unfolded protein response (UPR
                  mt
                  ) pathways have been extensively characterized in acute, genetic, and sustained models of mitochondrial perturbation, this work reveals how mitochondrial communication actively engages ER proteostasis during progressive and persistent metabolic stress. By expanding proteostatic capacity while tempering terminal stress signaling, MOTS-c enables cells to withstand chronic stress. Together, these findings define a MOTS-c-dependent arm of the MSR that integrates mitochondrial communication with ER proteostasis to promote chronic metabolic stress adaptation.
                
]]></description>
<dc:creator><![CDATA[ Bwiza, C., Schwab, E., Xia, L., Chen, A., Song, E., Lin, S., Kim, E., Hashiyada, Y., Son, J., Rice, M., Kim, J., Martins, S., Koh, E., Benayoun, B., Lee, C. ]]></dc:creator>
<dc:date>2026-6-23</dc:date>
<dc:identifier>doi:10.64898/2026.06.22.733272</dc:identifier>
<dc:title><![CDATA[MOTS-c Coordinates Inter-Organellar Proteostasis for Adaptation to Chronic Metabolic Stress]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-23</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.22.733265v1?rss=1">
<title>
<![CDATA[
Human cardiomyocytes with trisomy 21 exhibit heightened susceptibility and immunological response to SARS-CoV-2 infection 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.22.733265v1?rss=1
</link>
<description><![CDATA[

                
                  Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is associated with significant cardiovascular complications, including myocardial injury and long-term cardiac dysfunction. Individuals with Down syndrome (trisomy 21) exhibit increased susceptibility to severe COVID-19 outcomes, yet the cardiomyocyte-intrinsic mechanisms underlying this vulnerability remain poorly understood. To investigate genotype-specific responses to SARS-CoV-2 infection, we generated induced pluripotent stem cell–derived cardiomyocytes from individuals with trisomy 21 and their euploid, sex-matched biological relatives. Cardiomyocytes were inoculated with SARS-CoV-2, and viral susceptibility was assessed by immunofluorescence. Bulk RNA sequencing was performed under baseline and infected conditions to define transcriptional programs associated with viral response. Trisomy 21 iPSC-CMs exhibited increased susceptibility to SARS-CoV-2 infection, with greater viral protein expression and a higher proportion of infected cardiomyocytes compared to controls. Baseline transcriptomic analysis revealed no significant differences in canonical viral entry factors including
                  ACE2
                  and
                  TMPRSS2
                  , suggesting that differential susceptibility is not driven by entry receptor availability. Following infection, both trisomy 21 and euploid control groups activated conserved antiviral pathways; however, trisomy 21 cardiomyocytes displayed a markedly amplified transcriptional response, with substantially greater numbers of differentially expressed genes. Upregulated pathways included interferon signaling, NF-κB activation, cytokine and chemokine signaling, and innate immune responses, while downregulated pathways were enriched for cardiomyocyte structural integrity, calcium handling, and metabolic processes. Notably, inflammatory and cytokine-related transcripts were significantly more elevated in trisomy 21 cells, consistent with an exaggerated immune response. These findings provide mechanistic insight into the increased cardiovascular risk observed in individuals with Down syndrome and highlight dysregulated immune signaling as a potential therapeutic target in this high-risk population.
                
]]></description>
<dc:creator><![CDATA[ Alonzo, M., Mahesh, K., Wang, C., Wang, J., Bering, J., Ma, Q., Garg, V., Peeples, M., Zhao, M. ]]></dc:creator>
<dc:date>2026-6-22</dc:date>
<dc:identifier>doi:10.64898/2026.06.22.733265</dc:identifier>
<dc:title><![CDATA[Human cardiomyocytes with trisomy 21 exhibit heightened susceptibility and immunological response to SARS-CoV-2 infection]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.22.733769v1?rss=1">
<title>
<![CDATA[
Regulated conformational transitions in seipin define a functional ER–lipid droplet interface 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.22.733769v1?rss=1
</link>
<description><![CDATA[

                  Lipid droplets (LDs) are key organelles in cellular lipid homeostasis that form at the endoplasmic reticulum (ER) through a sequence of membrane rearrangements. While seipin emerged as an essential protein complex for LD biogenesis, how seipin-mediated LD formation proceeds beyond the initial step of neutral lipid nucleation remains unknown. Using a combination of
                  in vitro
                  and in-cell cryogenic electron microscopy (cryo-EM), ultrastructural expansion microscopy, molecular simulations and tailored genetic perturbations, we show that the seipin transmembrane domains undergo large-scale conformational rearrangements that define the architecture of the ER-LD interface and enable LD growth. Cryo-EM of purified
                  Xenopus
                  seipin revealed coexistence of two states: a compact “closed” conformation, consistent with early LD biogenesis, and an “open” conformation in which the transmembrane helices splay out laterally. Molecular dynamics simulations indicate that this open state induces local membrane curvature and promotes triacylglycerol accumulation. We identify conserved flexible linkers between the seipin luminal and transmembrane regions that act as mechanical hinges, enabling this conformational transition. We demonstrate that mutations in these hinge regions hinder seipin opening and affect LD formation in yeast and human cells. Analysis of native ER-LD contacts in human cells using light microscopy and cryo-electron tomography confirms that the seipin complex opens to establish stereotypical ~21-nm necks connecting the ER bilayer and LD monolayer. Moreover, we identify the liver-enriched microprotein SMLR1 as an inhibitor of this seipin conformational transition, providing a regulatory mechanism for seipin-dependent lipid storage in a tissue-specific manner. Together, these data establish seipin opening as a key structural rearrangement at the ER-LD interface that is essential for LD biogenesis and growth.
                
]]></description>
<dc:creator><![CDATA[ Salo, V., Klug, Y., Sapia, J., Deme, J., Tocci, J., Babenko, A., Jacob, R., Eikmeier, N., Zagoriy, E., Goetz, S., Campomanes, P., Banterle, N., Lea, S., Vanni, S., Carvalho, P., Mahamid, J. ]]></dc:creator>
<dc:date>2026-6-23</dc:date>
<dc:identifier>doi:10.64898/2026.06.22.733769</dc:identifier>
<dc:title><![CDATA[Regulated conformational transitions in seipin define a functional ER–lipid droplet interface]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-23</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.22.733702v1?rss=1">
<title>
<![CDATA[
SERCA2b loss of function drives pigmentation by inducing adaptive ER stress and enhancing mitochondrial calcium uptake: significance in pathological hyperpigmentation associated with Darier’s Disease 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.22.733702v1?rss=1
</link>
<description><![CDATA[

                Pigmentation is a critical protective mechanism that safeguards the skin against UV-induced damage, whereas dysregulated pigmentation predisposes to pigmentary disorders and skin malignancies. Although calcium signaling has emerged as an important regulator of melanogenesis, the identity of the calcium-handling proteins and the molecular mechanisms linking calcium dynamics to pigmentation remain poorly understood. Here, we identify the ER calcium pump SERCA2b as a negative regulator of pigmentation through modulation of ER stress and mitochondrial calcium uptake. We demonstrate that SERCA2b expression inversely correlates with pigmentation levels, and gain- and loss-of-function studies establish SERCA2b as a suppressor of melanogenesis. Mechanistically, SERCA2b depletion induces adaptive ER stress, enhances ER–mitochondrial proximity, and promotes mitochondrial calcium uptake. Notably, mutations in SERCA2b are associated with Darier disease, a condition characterized by hyperpigmented skin lesions, although the underlying mechanism remains unknown. To address this, we generated SERCA2b mutants corresponding to variants identified in Indian Darier’s disease patients and examined their effects on pigmentation, ER stress, and mitochondrial calcium dynamics. The mutant phenotypes closely recapitulated SERCA2b loss-of-function effects, demonstrating that adaptive ER stress and enhanced mitochondrial calcium signaling underlie hyperpigmentation associated with Darier’s disease. Importantly, treatment with 4-phenylbutyrate (4-PBA), an FDA-approved ER stress alleviator, rescued mutant-induced hyperpigmentation, reduced ER stress, and normalized mitochondrial calcium uptake. Collectively, our findings uncover a previously unrecognized role of SERCA2b in skin pigmentation, establish a mechanistic link between SERCA2b mutations and hyperpigmentation, and identify adaptive ER stress pathways as potential therapeutic target for pigmentary disorders.
]]></description>
<dc:creator><![CDATA[ Sharma, A., Saurav, S., Sharma, P., Agrawal, A., Sharma, N., Rajan, G., Bhalla, D., Pandhi, D., Yenamandra, V., Tanwar, J., Motiani, R. ]]></dc:creator>
<dc:date>2026-6-23</dc:date>
<dc:identifier>doi:10.64898/2026.06.22.733702</dc:identifier>
<dc:title><![CDATA[SERCA2b loss of function drives pigmentation by inducing adaptive ER stress and enhancing mitochondrial calcium uptake: significance in pathological hyperpigmentation associated with Darier’s Disease]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-23</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.22.733693v1?rss=1">
<title>
<![CDATA[
A humanized ossicle platform for real-time tracking and preclinical assessment of CAR-based immunotherapies in acute myeloid leukemia 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.22.733693v1?rss=1
</link>
<description><![CDATA[

                Preclinical evaluation of chimeric antigen receptor (CAR)-T therapies for acute myeloid leukemia (AML) is limited by the lack of models that faithfully recapitulate the human bone marrow (BM) niche. Here, we implemented a humanized ossicle-based AML model that enables simultaneous engraftment of leukemic blasts and longitudinal assessment of responses to CAR-based immunotherapies. Intravenous or intra-ossicle injection of AML blasts produced robust, reproducible disease mimicking features of human AML within its microenvironment. To monitor tumor burden and immune effector cells in real-time, we developed a dual bioluminescence system using distinct luciferases in AML and CAR-T cells. This approach allowed non-invasive longitudinal tracking of CAR-T cell localization, expansion, persistence, and leukemic clearance within the ossicle. Overall, our model provides a powerful platform to study CAR-T cell behavior within a human BM niche and, for the first time, allows simultaneous longitudinal visualization of leukemic burden and CAR-T cell dynamics in a physiologically relevant ossicle-based AML model.
                
                  Teaser
                  Humanized ossicles combined with dual BLI enable tracking of AML progression and CAR-T cell dynamics in a human stromal niche.
                
]]></description>
<dc:creator><![CDATA[ Donsante, S., Algeri, M., Biondi, M., Zambelli, V., Guzzetti, C., Grassenis, E., Alberti, G., Rezoagli, E., Tettamanti, S., Biondi, A., Riminucci, M., Pievani, A., Serafini, M. ]]></dc:creator>
<dc:date>2026-6-23</dc:date>
<dc:identifier>doi:10.64898/2026.06.22.733693</dc:identifier>
<dc:title><![CDATA[A humanized ossicle platform for real-time tracking and preclinical assessment of CAR-based immunotherapies in acute myeloid leukemia]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-23</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.22.733676v1?rss=1">
<title>
<![CDATA[
A GPX4 phosphorylation switch by FGFR1 guards against ferroptosis 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.22.733676v1?rss=1
</link>
<description><![CDATA[
SUMMARY
                
                  Ferroptosis is driven by lipid peroxidation, yet the mechanisms by which cells rapidly adjust their sensitivity to ferroptosis in response to extracellular cues remain elusive. We identify a direct phosphorylation switch controlling the activity of glutathione peroxidase 4 (GPX4), the core ferroptosis regulator. The receptor tyrosine kinase FGFR1 directly binds and phosphorylates GPX4 at Tyr180/Tyr196 in a kinase-dependent manner, requiring its Tyr730 as a docking site. This phosphorylation enhances GPX4’s catalytic activity and suppresses ferroptosis. In cardiac ischemia/reperfusion injury, the FGFR1-GPX4 axis is suppressed, and a selective FGFR1 agonist (FGF-1
                  ΔNT
                  ) reactivates it to protect against ferroptosis-mediated damage. Critically, a phosphorylation-deficient GPX4 knock-in mouse exhibits hypersensitivity to injury and non-responsive to this agonist, proving that GPX4 phosphorylation is essential. Our findings reveal a rapid mechanism for regulating ferroptosis via GPX4 tyrosine phosphorylation, directly linking receptor tyrosine kinase signaling to ferroptosis, and offering new strategies for treating ischemic-and other ferroptosis-associated diseases.
                
]]></description>
<dc:creator><![CDATA[ Song, L., Wang, L., Dong, W., Qi, J., Chen, J., Xu, S., Lu, H., Hou, Y., Ye, H., Tian, S., Qian, Q., Zhi, S., Sun, Y., Xi, J., Liang, W., Bai, F., Fan, L., Li, X., Huang, Z. ]]></dc:creator>
<dc:date>2026-6-23</dc:date>
<dc:identifier>doi:10.64898/2026.06.22.733676</dc:identifier>
<dc:title><![CDATA[A GPX4 phosphorylation switch by FGFR1 guards against ferroptosis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-23</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.21.730079v1?rss=1">
<title>
<![CDATA[
Physics-aware measurement-supervised deep learning enables point spread function inversion in soft X-ray tomography 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.21.730079v1?rss=1
</link>
<description><![CDATA[

                Soft X-ray tomography (SXT) is an emerging modality for whole-cell 3D imaging in near-native states. However, the effective spatial resolution is limited by optical artifacts characterized by the point spread function (PSF). To achieve optimal resolution via PSF inversion, we propose a measurement-supervised deep learning framework. Bypassing purely data-driven neural networks that are prone to hallucinations, we employ a measurement-supervised, instance-specific optimization strategy strictly constrained by a differentiable SXT formation forward model. The structural fidelity was validated using split-tilt Fourier ring correlation (FRC), ensuring the recovered high-frequency features reflect genuine specimen features rather than random artifacts. Our results demonstrate that this optimization consistently increases FRC resolution and enhances visual ultrastructural details across diverse biological structures. Furthermore, by recovering high-frequency features from sparse-angular projections, we show that spatial resolution can be maintained using only half the radiation exposure. This approach effectively compensates for the degradations caused by angular sparsity, providing a hardware-free computational solution to minimize radiation damage, maximize imaging speed, and overcome the optical and dosimetric limits of SXT.
]]></description>
<dc:creator><![CDATA[ Chueh, S., Capelle, C., Luo, L., Ishikawa, T., Evans, C., Fletcher, N., Lopez-Perez, M., Rogers, D., O'Connor, S., McIntyre, C., Donnellan, M., Simpson, J., Kapishnikov, S. ]]></dc:creator>
<dc:date>2026-6-23</dc:date>
<dc:identifier>doi:10.64898/2026.06.21.730079</dc:identifier>
<dc:title><![CDATA[Physics-aware measurement-supervised deep learning enables point spread function inversion in soft X-ray tomography]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-6-23</prism:publicationDate>
<prism:section></prism:section>
</item>
</rdf:RDF>
