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Unveiling the cell biology of hippocampal neurons with dendritic axon origin. 揭示具有树突轴突起源的海马神经元的细胞生物学。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-01-06 Epub Date: 2024-11-04 DOI: 10.1083/jcb.202403141
Yuhao Han, Daniela Hacker, Bronte Catharina Donders, Christopher Parperis, Roland Thuenauer, Christophe Leterrier, Kay Grünewald, Marina Mikhaylova
{"title":"Unveiling the cell biology of hippocampal neurons with dendritic axon origin.","authors":"Yuhao Han, Daniela Hacker, Bronte Catharina Donders, Christopher Parperis, Roland Thuenauer, Christophe Leterrier, Kay Grünewald, Marina Mikhaylova","doi":"10.1083/jcb.202403141","DOIUrl":"10.1083/jcb.202403141","url":null,"abstract":"<p><p>In mammalian axon-carrying-dendrite (AcD) neurons, the axon emanates from a basal dendrite, instead of the soma, to create a privileged route for action potential generation at the axon initial segment (AIS). However, it is unclear how such unusual morphology is established and whether the structure and function of the AIS in AcD neurons are preserved. By using dissociated hippocampal cultures as a model, we show that the development of AcD morphology can occur prior to synaptogenesis and independently of the in vivo environment. A single precursor neurite first gives rise to the axon and then to the AcD. The AIS possesses a similar cytoskeletal architecture as the soma-derived AIS and similarly functions as a trafficking barrier to retain axon-specific molecular composition. However, it does not undergo homeostatic plasticity, contains lesser cisternal organelles, and receives fewer inhibitory inputs. Our findings reveal insights into AcD neuron biology and underscore AIS structural differences based on axon onset.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568695","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}
引用次数: 0
Ca2+ tunneling architecture and function are important for secretion. Ca2+ 隧道结构和功能对分泌非常重要。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-01-06 Epub Date: 2024-11-05 DOI: 10.1083/jcb.202402107
Raphael J Courjaret, Larry E Wagner, Rahaf R Ammouri, David I Yule, Khaled Machaca
{"title":"Ca2+ tunneling architecture and function are important for secretion.","authors":"Raphael J Courjaret, Larry E Wagner, Rahaf R Ammouri, David I Yule, Khaled Machaca","doi":"10.1083/jcb.202402107","DOIUrl":"10.1083/jcb.202402107","url":null,"abstract":"<p><p>Ca2+ tunneling requires both store-operated Ca2+ entry (SOCE) and Ca2+ release from the endoplasmic reticulum (ER). Tunneling expands the SOCE microdomain through Ca2+ uptake by SERCA into the ER lumen where it diffuses and is released via IP3 receptors. In this study, using high-resolution imaging, we outline the spatial remodeling of the tunneling machinery (IP3R1; SERCA; PMCA; and Ano1 as an effector) relative to STIM1 in response to store depletion. We show that these modulators redistribute to distinct subdomains laterally at the plasma membrane (PM) and axially within the cortical ER. To functionally define the role of Ca2+ tunneling, we engineered a Ca2+ tunneling attenuator (CaTAr) that blocks tunneling without affecting Ca2+ release or SOCE. CaTAr inhibits Cl- secretion in sweat gland cells and reduces sweating in vivo in mice, showing that Ca2+ tunneling is important physiologically. Collectively our findings argue that Ca2+ tunneling is a fundamental Ca2+ signaling modality.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583387","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}
引用次数: 0
Heterogeneity of late endosome/lysosomes shown by multiplexed DNA-PAINT imaging. 多重 DNA-PAINT 成像显示晚期内膜体/溶酶体的异质性。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-01-06 Epub Date: 2024-11-01 DOI: 10.1083/jcb.202403116
Charles Bond, Siewert Hugelier, Jiazheng Xing, Elena M Sorokina, Melike Lakadamyali
{"title":"Heterogeneity of late endosome/lysosomes shown by multiplexed DNA-PAINT imaging.","authors":"Charles Bond, Siewert Hugelier, Jiazheng Xing, Elena M Sorokina, Melike Lakadamyali","doi":"10.1083/jcb.202403116","DOIUrl":"10.1083/jcb.202403116","url":null,"abstract":"<p><p>Late endosomes/lysosomes (LELs) are crucial for numerous physiological processes and their dysfunction is linked to many diseases. Proteomic analyses have identified hundreds of LEL proteins; however, whether these proteins are uniformly present on each LEL, or if there are cell-type-dependent LEL subpopulations with unique protein compositions is unclear. We employed quantitative, multiplexed DNA-PAINT super-resolution imaging to examine the distribution of seven key LEL proteins (LAMP1, LAMP2, CD63, Cathepsin D, TMEM192, NPC1, and LAMTOR4). While LAMP1, LAMP2, and Cathepsin D were abundant across LELs, marking a common population, most analyzed proteins were associated with specific LEL subpopulations. Our multiplexed imaging approach identified up to eight different LEL subpopulations based on their unique membrane protein composition. Additionally, our analysis of the spatial relationships between these subpopulations and mitochondria revealed a cell-type-specific tendency for NPC1-positive LELs to be closely positioned to mitochondria. Our approach will be broadly applicable to determining organelle heterogeneity with single organelle resolution in many biological contexts.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11533445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557909","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}
引用次数: 0
Postsynaptic BMP signaling regulates myonuclear properties in Drosophila larval muscles. 突触后BMP信号调节果蝇幼虫肌肉的肌核特性。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-01-06 Epub Date: 2024-10-30 DOI: 10.1083/jcb.202404052
Victoria E von Saucken, Stefanie E Windner, Giovanna Armetta, Mary K Baylies
{"title":"Postsynaptic BMP signaling regulates myonuclear properties in Drosophila larval muscles.","authors":"Victoria E von Saucken, Stefanie E Windner, Giovanna Armetta, Mary K Baylies","doi":"10.1083/jcb.202404052","DOIUrl":"10.1083/jcb.202404052","url":null,"abstract":"<p><p>The syncytial mammalian muscle fiber contains a heterogeneous population of (myo)nuclei. At the neuromuscular junction (NMJ), myonuclei have specialized positioning and gene expression. However, it remains unclear how myonuclei are recruited and what regulates myonuclear output at the NMJ. Here, we identify specific properties of myonuclei located near the Drosophila larval NMJ. These synaptic myonuclei have increased size in relation to their surrounding cytoplasmic domain (size scaling), increased DNA content (ploidy), and increased levels of transcription factor pMad, a readout for BMP signaling activity. Our genetic manipulations show that local BMP signaling affects muscle size, nuclear size, ploidy, and NMJ size and function. In support, RNA sequencing analysis reveals that pMad regulates genes involved in muscle growth, ploidy (i.e., E2f1), and neurotransmission. Our data suggest that muscle BMP signaling instructs synaptic myonuclear output that positively shapes the NMJ synapse. This study deepens our understanding of how myonuclear heterogeneity supports local signaling demands to fine tune cellular function and NMJ activity.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545720","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}
引用次数: 0
Definition of phosphatidylinositol 4,5-bisphosphate distribution by freeze-fracture replica labeling. 通过冷冻断裂复制标记确定磷脂酰肌醇 4,5-二磷酸的分布。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-01-06 Epub Date: 2024-11-04 DOI: 10.1083/jcb.202311067
Takuma Tsuji, Junya Hasegawa, Takehiko Sasaki, Toyoshi Fujimoto
{"title":"Definition of phosphatidylinositol 4,5-bisphosphate distribution by freeze-fracture replica labeling.","authors":"Takuma Tsuji, Junya Hasegawa, Takehiko Sasaki, Toyoshi Fujimoto","doi":"10.1083/jcb.202311067","DOIUrl":"10.1083/jcb.202311067","url":null,"abstract":"<p><p>Phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] is a phospholipid essential for plasma membrane functions, but its two-dimensional distribution is not clear. Here, we compared the result of sodium dodecyl sulfate-treated freeze-fracture replica labeling (SDS-FRL) of quick-frozen cells with the actual PtdIns(4,5)P2 content and the results obtained by fluorescence biosensor and by labeling of chemically-fixed membranes. In yeast, enrichment of PtdIns(4,5)P2 in the membrane compartment of Can1 (MCC)/eisosome, especially in the curved MCC/eisosome, was evident by SDS-FRL, but not by fluorescence biosensor, GFP-PLC1δ-PH. PtdIns(4,5)P2 remaining after acute ATP depletion and in the stationary phase, 30.0% and 56.6% of the control level, respectively, was not detectable by fluorescence biosensor, whereas the label intensity by SDS-FRL reflected the PtdIns(4,5)P2 amount. In PC12 cells, PtdIns(4,5)P2 was observed in a punctate pattern in the formaldehyde-fixed plasma membrane, whereas it was distributed randomly by SDS-FRL and showed clustering after formaldehyde fixation. The results indicate that the distribution of PtdIns(4,5)P2 can be defined most reliably by SDS-FRL of quick-frozen cells.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568691","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}
引用次数: 0
PINK1 controls RTN3L-mediated ER autophagy by regulating peripheral tubule junctions. PINK1 通过调节外周小管连接控制 RTN3L 介导的 ER 自噬。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2024-12-02 Epub Date: 2024-11-18 DOI: 10.1083/jcb.202407193
Ravi Chidambaram, Kamal Kumar, Smriti Parashar, Gowsalya Ramachandran, Shuliang Chen, Susan Ferro-Novick
{"title":"PINK1 controls RTN3L-mediated ER autophagy by regulating peripheral tubule junctions.","authors":"Ravi Chidambaram, Kamal Kumar, Smriti Parashar, Gowsalya Ramachandran, Shuliang Chen, Susan Ferro-Novick","doi":"10.1083/jcb.202407193","DOIUrl":"https://doi.org/10.1083/jcb.202407193","url":null,"abstract":"<p><p>Here, we report that the RTN3L-SEC24C endoplasmic reticulum autophagy (ER-phagy) receptor complex, the CUL3KLHL12 E3 ligase that ubiquitinates RTN3L, and the FIP200 autophagy initiating protein, target mutant proinsulin (Akita) condensates for lysosomal delivery at ER tubule junctions. When delivery was blocked, Akita condensates accumulated in the ER. In exploring the role of tubulation in these events, we unexpectedly found that loss of the Parkinson's disease protein, PINK1, reduced peripheral tubule junctions and blocked ER-phagy. Overexpression of the PINK1 kinase substrate, DRP1, increased junctions, reduced Akita condensate accumulation, and restored lysosomal delivery in PINK1-depleted cells. DRP1 is a dual-functioning protein that promotes ER tubulation and severs mitochondria at ER-mitochondria contact sites. DRP1-dependent ER tubulating activity was sufficient for suppression. Supporting these findings, we observed PINK1 associating with ER tubules. Our findings show that PINK1 shapes the ER to target misfolded proinsulin for RTN3L-SEC24C-mediated macro-ER-phagy at defined ER sites called peripheral junctions. These observations may have important implications for understanding Parkinson's disease.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 12","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648187","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}
引用次数: 0
Stairway to the Golgi: Two paths VPS13B can go by. 通往高尔基体的阶梯VPS13B 有两条路可走
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2024-12-02 Epub Date: 2024-11-12 DOI: 10.1083/jcb.202411005
Roger Pons Lanau, Felix Campelo
{"title":"Stairway to the Golgi: Two paths VPS13B can go by.","authors":"Roger Pons Lanau, Felix Campelo","doi":"10.1083/jcb.202411005","DOIUrl":"10.1083/jcb.202411005","url":null,"abstract":"<p><p>VPS13 proteins mediate lipid transfer across membranes. Among them, VPS13B is associated with Golgi membranes, and VPS13B mutations cause Cohen syndrome. In this issue, Ugur et al. (https://doi.org/10.1083/jcb.202311189) and Du et al. (https://doi.org/10.1083/jcb.202402083) reveal new VPS13B interactors and their functions in Golgi organization and trafficking.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 12","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621218","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}
引用次数: 0
Visualizing ER-phagy and ER architecture in vivo. 体内ER吞噬和ER结构的可视化。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2024-12-02 Epub Date: 2024-11-18 DOI: 10.1083/jcb.202408061
Yongjuan Sang, Boran Li, Tinglin Su, Hanyu Zhan, Yue Xiong, Zhiming Huang, Changjing Wang, Xiaoxia Cong, Mengjie Du, Yang Wu, Hang Yu, Xi Yang, Kezhi Ding, Xuhua Wang, Xiaolong Miao, Weihua Gong, Liang Wang, Jingwei Zhao, Yiting Zhou, Wei Liu, Xinyang Hu, Qiming Sun
{"title":"Visualizing ER-phagy and ER architecture in vivo.","authors":"Yongjuan Sang, Boran Li, Tinglin Su, Hanyu Zhan, Yue Xiong, Zhiming Huang, Changjing Wang, Xiaoxia Cong, Mengjie Du, Yang Wu, Hang Yu, Xi Yang, Kezhi Ding, Xuhua Wang, Xiaolong Miao, Weihua Gong, Liang Wang, Jingwei Zhao, Yiting Zhou, Wei Liu, Xinyang Hu, Qiming Sun","doi":"10.1083/jcb.202408061","DOIUrl":"https://doi.org/10.1083/jcb.202408061","url":null,"abstract":"<p><p>ER-phagy is an evolutionarily conserved mechanism crucial for maintaining cellular homeostasis. However, significant gaps persist in our understanding of how ER-phagy and the ER network vary across cell subtypes, tissues, and organs. Furthermore, the pathophysiological relevance of ER-phagy remains poorly elucidated. Addressing these questions requires developing quantifiable methods to visualize ER-phagy and ER architecture in vivo. We generated two transgenic mouse lines expressing an ER lumen-targeting tandem RFP-GFP (ER-TRG) tag, either constitutively or conditionally. This approach enables precise spatiotemporal measurements of ER-phagy and ER structure at single-cell resolution in vivo. Systemic analysis across diverse organs, tissues, and primary cultures derived from these ER-phagy reporter mice unveiled significant variations in basal ER-phagy, both in vivo and ex vivo. Furthermore, our investigation uncovered substantial remodeling of ER-phagy and the ER network in different tissues under stressed conditions such as starvation, oncogenic transformation, and tissue injury. In summary, both reporter models represent valuable resources with broad applications in fundamental research and translational studies.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 12","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648286","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}
引用次数: 0
Non-cell autonomous regulation of cell-cell signaling and differentiation by mitochondrial ROS. 线粒体 ROS 对细胞-细胞信号传递和分化的非细胞自主调控。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2024-12-02 Epub Date: 2024-11-13 DOI: 10.1083/jcb.202401084
Yipeng Du, Lei Wang, Lizbeth Perez-Castro, Maralice Conacci-Sorrell, Matthew Sieber
{"title":"Non-cell autonomous regulation of cell-cell signaling and differentiation by mitochondrial ROS.","authors":"Yipeng Du, Lei Wang, Lizbeth Perez-Castro, Maralice Conacci-Sorrell, Matthew Sieber","doi":"10.1083/jcb.202401084","DOIUrl":"10.1083/jcb.202401084","url":null,"abstract":"<p><p>Mitochondrial reactive oxygen species (ROS) function intrinsically within cells to induce cell damage, regulate transcription, and cause genome instability. However, we know little about how mitochondrial ROS production non-cell autonomously impacts cell-cell signaling. Here, we show that mitochondrial dysfunction inhibits the plasma membrane localization of cell surface receptors that drive cell-cell communication during oogenesis. Within minutes, we found that mitochondrial ROS impairs exocyst membrane binding and leads to defective endosomal recycling. This endosomal defect impairs the trafficking of receptors, such as the Notch ligand Delta, during oogenesis. Remarkably, we found that overexpressing RAB11 restores ligand trafficking and rescues the developmental defects caused by ROS production. ROS production from adjacent cells acutely initiates a transcriptional response associated with growth and migration by suppressing Notch signaling and inducing extra cellualr matrix (ECM) remodeling. Our work reveals a conserved rapid response to ROS production that links mitochondrial dysfunction to the non-cell autonomous regulation of cell-cell signaling.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 12","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621213","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}
引用次数: 0
eIF5A controls mitoprotein import by relieving ribosome stalling at TIM50 translocase mRNA. eIF5A 通过缓解 TIM50 易位酶 mRNA 的核糖体停滞来控制有丝分裂蛋白的导入。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2024-12-02 Epub Date: 2024-11-07 DOI: 10.1083/jcb.202404094
Marina Barba-Aliaga, Vanessa Bernal, Cynthia Rong, Madeleine E Volfbeyn, Keguang Zhang, Brian M Zid, Paula Alepuz
{"title":"eIF5A controls mitoprotein import by relieving ribosome stalling at TIM50 translocase mRNA.","authors":"Marina Barba-Aliaga, Vanessa Bernal, Cynthia Rong, Madeleine E Volfbeyn, Keguang Zhang, Brian M Zid, Paula Alepuz","doi":"10.1083/jcb.202404094","DOIUrl":"10.1083/jcb.202404094","url":null,"abstract":"<p><p>Efficient import of nuclear-encoded proteins into mitochondria is crucial for proper mitochondrial function. The conserved translation factor eIF5A binds ribosomes, alleviating stalling at polyproline-encoding sequences. eIF5A impacts mitochondrial function across species, though the precise molecular mechanism is unclear. We found that eIF5A depletion in yeast reduces the translation and levels of the TCA cycle and oxidative phosphorylation proteins. Loss of eIF5A causes mitoprotein precursors to accumulate in the cytosol and triggers a mitochondrial import stress response. We identify an essential polyproline protein as a direct target of eIF5A: the mitochondrial inner membrane protein and translocase component Tim50. Thus, eIF5A controls mitochondrial protein import by alleviating ribosome stalling along Tim50 mRNA at the mitochondrial surface. Removal of polyprolines from Tim50 partially rescues the mitochondrial import stress response and translation of oxidative phosphorylation genes. Overall, our findings elucidate how eIF5A impacts the mitochondrial function by promoting efficient translation and reducing ribosome stalling of co-translationally imported proteins, thereby positively impacting the mitochondrial import process.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 12","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604896","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}
引用次数: 0
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