{"title":"Rab GTPases are evolutionarily conserved signals mediating selective autophagy.","authors":"Pengwei Zhao, Rui Tian, Dandan Song, Qi Zhu, Xianming Ding, Jianqin Zhang, Beibei Cao, Mengyuan Zhang, Yilu Xu, Jie Fang, Jieqiong Tan, Cong Yi, Hongguang Xia, Wei Liu, Wei Zou, Qiming Sun","doi":"10.1083/jcb.202410150","DOIUrl":"10.1083/jcb.202410150","url":null,"abstract":"<p><p>Selective autophagy plays a crucial role in maintaining cellular homeostasis by specifically targeting unwanted cargo labeled with \"autophagy cues\" signals for autophagic degradation. In this study, we identify Rab GTPases as a class of such autophagy cues signals involved in selective autophagy. Through biochemical and imaging screens, we reveal that human Rab GTPases are common autophagy substrates. Importantly, we confirm the conservation of Rab GTPase autophagic degradation in different model organisms. Rab GTPases translocate to damaged mitochondria, lipid droplets, and invading Salmonella-containing vacuoles (SCVs) to serve as degradation signals. Furthermore, they facilitate mitophagy, lipophagy, and xenophagy, respectively, by recruiting receptors. This interplay between Rab GTPases and receptors may ensure the de novo synthesis of isolation membranes around Rab-GTPase-labeled cargo, thereby mediating selective autophagy. These processes are further influenced by upstream regulators such as LRRK2, GDIs, and RabGGTase. In conclusion, this study unveils a conserved mechanism involving Rab GTPases as autophagy cues signals and proposes a model for the spatiotemporal control of selective autophagy.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of Cell BiologyPub Date : 2025-05-05Epub Date: 2025-04-10DOI: 10.1083/jcb.20240211404042025c
Alison C E Wirshing, Claudia A Petrucco, Daniel J Lew
{"title":"Correction: Chemical transformation of the multibudding yeast, Aureobasidium pullulans.","authors":"Alison C E Wirshing, Claudia A Petrucco, Daniel J Lew","doi":"10.1083/jcb.20240211404042025c","DOIUrl":"https://doi.org/10.1083/jcb.20240211404042025c","url":null,"abstract":"","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11984486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kunyou Park, Sungeun Ju, Hyewon Choi, Peng Gao, Geul Bang, Jung Hoon Choi, Jiwon Jang, Andrew J Morris, Byung-Ho Kang, Victor W Hsu, Seung-Yeol Park
{"title":"PITPβ promotes COPI vesicle fission through lipid transfer and membrane contact formation.","authors":"Kunyou Park, Sungeun Ju, Hyewon Choi, Peng Gao, Geul Bang, Jung Hoon Choi, Jiwon Jang, Andrew J Morris, Byung-Ho Kang, Victor W Hsu, Seung-Yeol Park","doi":"10.1083/jcb.202407166","DOIUrl":"https://doi.org/10.1083/jcb.202407166","url":null,"abstract":"<p><p>Intracellular transport among organellar compartments occurs in two general ways: by membrane-bound carriers and membrane contacts. Specific circumstances that involve the coordination of these two modes of transport remain to be defined. By studying coat protein I (COPI) transport, we find that phosphatidylcholine with short acyl chains (sPC) is delivered through membrane contact from the endoplasmic reticulum (ER) to sites of COPI vesicle formation at the Golgi to support the fission stage. Phosphatidylinositol transfer protein beta (PITPβ) plays a key role in this process, with the elucidation of this role shedding new insights into how PITPβ acts, providing a mechanistic understanding of a specific circumstance when vesicular transport requires membrane contact and contributing to the general understanding of how intracellular transport carriers are formed.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11987707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laura Trachsel-Moncho, Chiara Veroni, Benan John Mathai, Ana Lapao, Sakshi Singh, Nagham Theres Asp, Sebastian W Schultz, Serhiy Pankiv, Anne Simonsen
{"title":"SNX10 functions as a modulator of piecemeal mitophagy and mitochondrial bioenergetics.","authors":"Laura Trachsel-Moncho, Chiara Veroni, Benan John Mathai, Ana Lapao, Sakshi Singh, Nagham Theres Asp, Sebastian W Schultz, Serhiy Pankiv, Anne Simonsen","doi":"10.1083/jcb.202404009","DOIUrl":"10.1083/jcb.202404009","url":null,"abstract":"<p><p>We here identify the endosomal protein SNX10 as a negative regulator of piecemeal mitophagy of OXPHOS machinery components. In control conditions, SNX10 localizes to early endocytic compartments in a PtdIns3P-dependent manner and modulates endosomal trafficking but also shows dynamic connections with mitochondria. Upon hypoxia-mimicking conditions, SNX10 localizes to late endosomal structures containing selected mitochondrial proteins, including COX-IV and SAMM50, and the autophagy proteins SQSTM1/p62 and LC3B. The turnover of COX-IV was enhanced in SNX10-depleted cells, with a corresponding reduced mitochondrial respiration and citrate synthase activity. Importantly, zebrafish larvae lacking Snx10 show reduced levels of Cox-IV, as well as elevated ROS levels and ROS-mediated cell death in the brain, demonstrating the in vivo relevance of SNX10-mediated modulation of mitochondrial bioenergetics.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Vacuoles provide the source membrane for TORC1-containing signaling endosomes.","authors":"Kenji Muneshige, Riko Hatakeyama","doi":"10.1083/jcb.202407021","DOIUrl":"10.1083/jcb.202407021","url":null,"abstract":"<p><p>Organelle biogenesis is fundamental to eukaryotic cell biology. Yeast signaling endosomes were recently identified as a signaling platform for the evolutionarily conserved Target of Rapamycin Complex 1 (TORC1) kinase complex. Despite the importance of signaling endosomes for TORC1-mediated control of cellular metabolism, how this organelle is generated has been a mystery. Here, we developed a system to induce synchronized de novo formation of signaling endosomes, enabling real-time monitoring of their biogenesis. Using this system, we identify vacuoles as a membrane source for newly formed signaling endosomes. Membrane supply from vacuoles is mediated by the CROP membrane-cutting complex, consisting of Atg18 PROPPIN and retromer subunits. The formation of signaling endosomes requires TORC1 activity, suggestive of a tightly regulated process. This study unveiled the first mechanistic principles and molecular participants of signaling endosome biogenesis.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rhythmic TDP-43 affects RNA splicing of USP13, resulting in alteration of BMAL1 ubiquitination.","authors":"Jianlan Gu, Mingming Yang, Liti Zhang, Yuxiao Liu, Ruolan Yan, Danmin Pan, Xiaowei Qian, Hanjing Hu, Dandan Chu, Chen Hu, Fei Liu, Hengxiang Cui","doi":"10.1083/jcb.202405142","DOIUrl":"10.1083/jcb.202405142","url":null,"abstract":"<p><p>Circadian rhythm disorders are common characteristics of neurodegenerative diseases. The pathological aggregation of transactive response DNA-binding protein 43 (TDP-43) is associated with multiple neurodegenerative diseases, such as amyotrophic lateral sclerosis. However, the relationship between TDP-43 and circadian rhythm remains unknown. Here, we found that TDP-43 is rhythmically expressed both in vivo and in vitro. TDP-43 knockdown affected the expression of circadian genes, including BMAL1, CLOCK, CRY1, and PER2, and impaired autonomous circadian wheel behavior, cognitive functions, and balance abilities in mice. Furthermore, TDP-43 knockdown induced aberrant splicing of ubiquitin-specific peptidase 13 (USP13) and blocked USP13 rhythmic expression, enhancing the ubiquitination of BMAL1. Meanwhile, TDP-43 knockdown altered the rhythmic expression of phospho-AMPKα (Thr172) and platelet-type phosphofructokinase (PFKP), which may change cellular glucose uptake and ATP production. Our findings further the understanding of the role of TDP-43 dysfunction in circadian rhythm disruption in neurodegenerative diseases and provide new mechanistic evidence supporting the interaction between circadian rhythm disruption and neurodegeneration.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lauren E Vostal, Noa E Dahan, Matthew J Reynolds, Lily I Kronenberg, Tarun M Kapoor
{"title":"Structural insights into the coupling between VCP, an essential unfoldase, and a deubiquitinase.","authors":"Lauren E Vostal, Noa E Dahan, Matthew J Reynolds, Lily I Kronenberg, Tarun M Kapoor","doi":"10.1083/jcb.202410148","DOIUrl":"10.1083/jcb.202410148","url":null,"abstract":"<p><p>Proteostasis involves degradation and recycling of proteins from organelles, membranes, and multiprotein complexes. These processes can depend on protein extraction and unfolding by the essential mechanoenzyme valosin-containing protein (VCP) and on ubiquitin chain remodeling by ubiquitin-specific proteases known as deubiquitinases (DUBs). How the activities of VCP and DUBs are coordinated is poorly understood. Here, we focus on the DUB VCPIP1, a VCP interactor required for post-mitotic Golgi and ER organization. We determine ∼3.3 Å cryogenic electron microscopy structures of VCP-VCPIP1 complexes in the absence of added nucleotide or the presence of an ATP analog. We find that up to 3 VCPIP1 protomers interact with the VCP hexamer to position VCPIP1's catalytic domain at the exit of VCP's central pore, poised to cleave ubiquitin following substrate unfolding. We observe competition between VCPIP1 and other cofactors for VCP binding and show that VCP stimulates VCPIP1's DUB activity. Together, our data suggest how the two enzyme activities can be coordinated to regulate proteostasis.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuchieh Jay Lin, Li-Ting Huang, Po-Yuan Ke, Guang-Chao Chen
{"title":"The deubiquitinase USP45 inhibits autophagy through actin regulation by Coronin 1B.","authors":"Yuchieh Jay Lin, Li-Ting Huang, Po-Yuan Ke, Guang-Chao Chen","doi":"10.1083/jcb.202407014","DOIUrl":"10.1083/jcb.202407014","url":null,"abstract":"<p><p>The autophagy-lysosomal system comprises a highly dynamic and interconnected vesicular network that plays a central role in maintaining proteostasis and cellular homeostasis. In this study, we uncovered the deubiquitinating enzyme (DUB), dUsp45/USP45, as a key player in regulating autophagy and lysosomal activity in Drosophila and mammalian cells. Loss of dUsp45/USP45 results in autophagy activation and increased levels of V-ATPase to lysosomes, thus enhancing lysosomal acidification and function. Furthermore, we identified the actin-binding protein Coronin 1B (Coro1B) as a substrate of USP45. USP45 interacts with and deubiquitinates Coro1B, thereby stabilizing Coro1B levels. Notably, the ablation of USP45 or Coro1B promotes the formation of F-actin patches and the translocation of V-ATPase to lysosomes in an N-WASP-dependent manner. Additionally, we observed positive effects of dUsp45 depletion on extending lifespan and ameliorating polyglutamine (polyQ)-induced toxicity in Drosophila. Our findings highlight the important role of dUsp45/USP45 in regulating lysosomal function by modulating actin structures through Coro1B.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of Cell BiologyPub Date : 2025-05-05Epub Date: 2025-04-04DOI: 10.1083/jcb.20240701403262025c
Yuchieh Jay Lin, Li-Ting Huang, Po-Yuan Ke, Guang-Chao Chen
{"title":"Correction: The deubiquitinase USP45 inhibits autophagy through actin regulation by Coronin 1B.","authors":"Yuchieh Jay Lin, Li-Ting Huang, Po-Yuan Ke, Guang-Chao Chen","doi":"10.1083/jcb.20240701403262025c","DOIUrl":"10.1083/jcb.20240701403262025c","url":null,"abstract":"","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A cortical pool of LIN-5 (NuMA) controls cytokinetic furrow formation and cytokinesis completion.","authors":"Kuheli Adhikary,Sukriti Kapoor,Sachin Kotak","doi":"10.1083/jcb.202406059","DOIUrl":"https://doi.org/10.1083/jcb.202406059","url":null,"abstract":"In animal cells, cleavage furrow formation is controlled by localized activation of the GTPase RhoA at the equatorial membrane using cues transmitted from the spindle. Here, we explore the function of LIN-5, a well-studied protein known for its role in aster separation and spindle positioning in cleavage furrow formation. We show that the cortical pool of LIN-5, recruited by GPR-1/2 and important for cortical force generation, regulates cleavage furrow formation independently of its roles in aster separation and spindle positioning. Instead, our data suggest that enrichment of LIN-5/GPR-1/2 at the polar cortical region is essential to ensure the timely accumulation of contractile ring components-myosin II and Anillin at the equatorial cortex. We additionally define a late cytokinesis role of cortical LIN-5/GPR-1/2 in midbody stabilization and abscission. These results indicate that the cortical LIN-5/GPR-1/2 complex contributes to multiple aspects of cytokinesis independently of its roles in spindle positioning and elongation.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"418 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}