Journal of cell science最新文献_第5页

The role of mitochondrial mRNA translation in cellular communication. 线粒体mRNA翻译在细胞通讯中的作用。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-01 Epub Date: 2025-05-06 DOI: 10.1242/jcs.263753

Eleonora Zilio, Tim Schlegel, Marta Zaninello, Elena I Rugarli

{"title":"The role of mitochondrial mRNA translation in cellular communication.","authors":"Eleonora Zilio, Tim Schlegel, Marta Zaninello, Elena I Rugarli","doi":"10.1242/jcs.263753","DOIUrl":"https://doi.org/10.1242/jcs.263753","url":null,"abstract":"Mitochondria are dynamic and heterogeneous organelles that rewire their network and metabolic functions in response to changing cellular needs. To this end, mitochondria integrate a plethora of incoming signals to influence cell fate and survival. A crucial and highly regulated node of cell-mitochondria communication is the translation of nuclear-encoded mitochondrial mRNAs. By controlling and monitoring the spatio-temporal translation of these mRNAs, cells can rapidly adjust mitochondrial function to meet metabolic demands, optimise ATP production and regulate organelle biogenesis and turnover. In this Review, we focus on how RNA-binding proteins that recognise nuclear-encoded mitochondrial mRNAs acutely modulate the rate of translation in response to nutrient availability. We further discuss the relevance of localised translation of these mRNAs for subsets of mitochondria in polarised cells. Finally, we highlight quality control mechanisms that monitor the translation process at the mitochondrial surface and their connections to mitophagy and stress responses. We propose that these processes collectively contribute to mitochondrial specialisation and signalling function.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 9","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

A lipid in transit - the journey of cholesterol into the heart of mitochondrial research. 运输中的脂质——胆固醇进入线粒体研究核心的旅程。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-01 Epub Date: 2025-05-08 DOI: 10.1242/jcs.263907

Thomas Simmen, Luca Pellegrini

{"title":"A lipid in transit - the journey of cholesterol into the heart of mitochondrial research.","authors":"Thomas Simmen, Luca Pellegrini","doi":"10.1242/jcs.263907","DOIUrl":"https://doi.org/10.1242/jcs.263907","url":null,"abstract":"Mitochondrial cholesterol biology in non-steroidogenic tissues remains understudied in cell science. Although detecting cholesterol in mitochondria is challenging due to isolation difficulties, studies using mitoplasts (mitochondria stripped of their outer membrane) and imaging approaches confirm its presence in the inner mitochondrial membrane. Through analysis of published evidence and first-principles reasoning, we advance a model of cholesterol trafficking into and out of mitochondria via phospholipids at mitochondria-associated membranes (MAMs), challenging the traditional view of protein-driven transport. In this model, cholesterol enters mitochondria alongside phosphatidylserine and exits with phosphatidylethanolamine - either unchanged or in a hydroxylated form after modification by the enzyme CYP27A1. Strong cholesterol-phospholipid binding energies, ∼17 kcal/mol (71.128 kJ/mol), support this lipid-mediated mechanism, suggesting it complements protein-based pathways. Future research should explore how these mechanisms collaborate to regulate mitochondrial cholesterol trafficking. By rethinking cholesterol dynamics, we raise the possibility that cholesterol plays a larger role in mitochondrial biology, influencing membrane-dependent functions like cristae structure, respiratory efficiency and inter-organelle communication. This Perspective also highlights the potential of mitochondria to regulate both dietary and endogenous cholesterol flux and homeostasis across the cell.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 9","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Integrated proteome and lipidome analyses place OCIAD1 at the mitochondria-peroxisome intersection balancing lipid metabolism. 综合蛋白质组学和脂质组学分析发现OCIAD1位于线粒体-过氧化物酶体的交叉点，平衡脂质代谢。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-01 Epub Date: 2025-05-09 DOI: 10.1242/jcs.263729

Vanessa Linke, Mateusz Chodkowski, Kacper Kaszuba, Mariusz Radkiewicz, Tina A Schrader, Hirak Das, Vikas Rana, Dorota Stadnik, Michał Dadlez, Bettina Warscheid, Michael Schrader, Agnieszka Chacinska

{"title":"Integrated proteome and lipidome analyses place OCIAD1 at the mitochondria-peroxisome intersection balancing lipid metabolism.","authors":"Vanessa Linke, Mateusz Chodkowski, Kacper Kaszuba, Mariusz Radkiewicz, Tina A Schrader, Hirak Das, Vikas Rana, Dorota Stadnik, Michał Dadlez, Bettina Warscheid, Michael Schrader, Agnieszka Chacinska","doi":"10.1242/jcs.263729","DOIUrl":"https://doi.org/10.1242/jcs.263729","url":null,"abstract":"Ovarian cancer immunoreactive antigen domain-containing 1 (OCIAD1) is a membrane protein largely localized to mitochondria; however, its function in health or disease is not well understood. To comprehensively characterize the molecular changes upon lack of OCIAD1, we used mass spectrometry to study the mitochondrial and cellular proteome and lipidome. We show that there is extensive lipidome rearrangement in OCIAD1 knockout (KO) cells, characterized by two main phenotypes of decreased levels of ether phospholipids and decreased levels of phospholipids with an odd number of carbons. The lipidomic changes suggest alterations in peroxisomal lipid metabolism. At the same time, proteins responsible for mitochondrial fatty acid β-oxidation are significantly increased. Together with a global loss in peroxisomal proteins, aberrant peroxisomal morphology, and a meta-analysis of proximity labeling data, this gives a function to the previously observed partial localization of OCIAD1 to peroxisomes. We suggest a role for OCIAD1 in balancing mitochondrial and peroxisomal lipid metabolism, and a direct impact on the key enzymes FAR1 and ABCD3.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 9","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Special Issue - Cell Biology of Mitochondria. 特刊-线粒体细胞生物学。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-01 Epub Date: 2025-05-14 DOI: 10.1242/jcs.264067

Ana J Garcia-Saez, Heidi McBride

引用次数: 0

Regulation of mitochondrial cristae organization by Myo19, Miro1 and Miro2, and metaxin 3. Myo19、Miro1/2和Metaxin 3对线粒体嵴组织的调控。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-01 Epub Date: 2025-03-06 DOI: 10.1242/jcs.263637

Samruddhi S Shembekar, Petra Nikolaus, Ulrike Honnert, Marcus Höring, Aya Attia, Karin Topp, Birgit Lohmann, Gerhard Liebisch, Martin Bähler

{"title":"Regulation of mitochondrial cristae organization by Myo19, Miro1 and Miro2, and metaxin 3.","authors":"Samruddhi S Shembekar, Petra Nikolaus, Ulrike Honnert, Marcus Höring, Aya Attia, Karin Topp, Birgit Lohmann, Gerhard Liebisch, Martin Bähler","doi":"10.1242/jcs.263637","DOIUrl":"10.1242/jcs.263637","url":null,"abstract":"The actin-based motor myosin-19 (Myo19) exerts force on mitochondrial membrane receptors Miro1/2, influencing endoplasmic reticulum (ER)-mitochondria contact sites and mitochondrial cristae structure. The mitochondrial intermembrane bridging (MIB) complex connects the outer and inner mitochondrial membranes at the cristae junction through the mitochondrial contact site and cristae organization system (MICOS). However, the interaction between Myo19, Miro1 and Miro2 (hereafter Miro1/2), and the MIB-MICOS complex in cristae regulation remains unclear. This study investigates the roles of Miro1/2 and metaxin 3 (Mtx3), a MIB complex component, in linking Myo19 to MIB-MICOS. We show that Miro1/2 interact with Myo19 and the MIB complex but not with Mtx3. Their mitochondrial membrane anchors are not essential for MIB interaction or cristae structure. However, Mtx3 is crucial for the connection between MIB-MICOS and the Myo19 and Miro1/2 proteins. Deleting Miro1/2 mimics the effects of Myo19 deficiency on ER-mitochondria contacts and cristae structure, whereas Mtx3 deletion does not. Notably, the loss of Myo19 and Miro1/2 alters mitochondrial lipid composition, reducing cardiolipin and its precursors, suggesting Myo19 and Miro1/2 influence cristae indirectly via lipid transfer at ER-mitochondria contact sites.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Approaches to reduce succinate accumulation by restoration of succinate dehydrogenase activity in cultured adrenal cells. 通过恢复培养肾上腺细胞中琥珀酸脱氢酶活性来减少琥珀酸积累的方法。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-01 Epub Date: 2025-05-12 DOI: 10.1242/jcs.263925

Fatimah Al Khazal, Leili Rahimi, Fan Feng, Nicole A Becker, Clifford D Folmes, Judith Favier, L James Maher

引用次数: 0

Activation of the mitochondrial unfolded protein response regulates the dynamic formation of stress granules. 线粒体未折叠蛋白反应的激活调节应激颗粒的动态形成。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-01 Epub Date: 2024-12-05 DOI: 10.1242/jcs.263548

Marta Lopez-Nieto, Zhaozhi Sun, Emily Relton, Rahme Safakli, Brian D Freibaum, J Paul Taylor, Alessia Ruggieri, Ioannis Smyrnias, Nicolas Locker

{"title":"Activation of the mitochondrial unfolded protein response regulates the dynamic formation of stress granules.","authors":"Marta Lopez-Nieto, Zhaozhi Sun, Emily Relton, Rahme Safakli, Brian D Freibaum, J Paul Taylor, Alessia Ruggieri, Ioannis Smyrnias, Nicolas Locker","doi":"10.1242/jcs.263548","DOIUrl":"10.1242/jcs.263548","url":null,"abstract":"To rapidly adapt to harmful changes to their environment, cells activate the integrated stress response (ISR). This results in an adaptive transcriptional and translational rewiring, and the formation of biomolecular condensates named stress granules (SGs), to resolve stress. In addition to this first line of defence, the mitochondrial unfolded protein response (UPRmt) activates a specific transcriptional programme to maintain mitochondrial homeostasis. We present evidence that the SG formation and UPRmt pathways are intertwined and communicate. UPRmt induction results in eIF2α phosphorylation and the initial and transient formation of SGs, which subsequently disassemble. The induction of GADD34 (also known as PPP1R15A) during late UPRmt protects cells from prolonged stress by impairing further assembly of SGs. Furthermore, mitochondrial functions and cellular survival are enhanced during UPRmt activation when SGs are absent, suggesting that UPRmt-induced SGs have an adverse effect on mitochondrial homeostasis. These findings point to a novel crosstalk between SGs and the UPRmt that might contribute to restoring mitochondrial functions under stressful conditions.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Miro1 expression alters global gene expression, ERK1/2 phosphorylation, oxidation and cell cycle progression. Miro1表达改变全局基因表达、ERK1/2磷酸化、氧化和细胞周期进程。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-01 Epub Date: 2025-04-02 DOI: 10.1242/jcs.263554

Nathaniel Shannon, Cory Raymond, Chloe Palmer, Silver Homa, Marcelo Bonini, David Seward, Brian Cunniff

{"title":"Miro1 expression alters global gene expression, ERK1/2 phosphorylation, oxidation and cell cycle progression.","authors":"Nathaniel Shannon, Cory Raymond, Chloe Palmer, Silver Homa, Marcelo Bonini, David Seward, Brian Cunniff","doi":"10.1242/jcs.263554","DOIUrl":"10.1242/jcs.263554","url":null,"abstract":"Mitochondrial positioning supports localized energy and signaling requirements. Miro1 is necessary for attachment of mitochondria to microtubule motor proteins for trafficking. When Miro1 is deleted (Miro1-/-) from mouse embryonic fibroblasts (MEFs), mitochondria become sequestered to the perinuclear space, disrupting subcellular signaling gradients. Here, we show that Miro1-/- MEFs grow slower than Miro1+/+ and Miro1-/- MEFs stably re-expressing a Myc-Miro1 plasmid. Miro1-/- MEFs have a decreased percentage of cells in G1 and increased percentage of cells in S phase. We conducted the first ever RNA sequencing experiment dependent upon Miro1 expression and found differentially expressed genes related to MAPK signaling, cell proliferation and migration. ERK1 and ERK2 (ERK1/2, also known as MAPK3 and MAPK1, respectively) phosphorylation is elevated both spatially and temporally following serum stimulation in Miro1-/- MEFs, whereas the expression levels and oxidation of the dual specificity phosphatases (DUSP1-DUSP6) is unchanged. Finally, we found the oxidation status of ERK1/2 is increased in Miro1-/- MEFs compared to that seen in Miro1+/+ and Myc-Miro1 MEFs. These results highlight transcriptional control based off Miro1 expression and demonstrate the dynamic regulation of ERK1/2 upon deletion of Miro1 which might support the observed cell cycle and proliferation defects.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Mitophagy is induced in human engineered heart tissue after simulated ischemia and reperfusion. 模拟心肌缺血再灌注后，人工程化心脏组织可诱导线粒体自噬。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-01 Epub Date: 2025-03-19 DOI: 10.1242/jcs.263408

Mireia Nàger, Kenneth B Larsen, Zambarlal Bhujabal, Trine B Kalstad, Judith Rössinger, Truls Myrmel, Florian Weinberger, Asa B Birgisdottir

{"title":"Mitophagy is induced in human engineered heart tissue after simulated ischemia and reperfusion.","authors":"Mireia Nàger, Kenneth B Larsen, Zambarlal Bhujabal, Trine B Kalstad, Judith Rössinger, Truls Myrmel, Florian Weinberger, Asa B Birgisdottir","doi":"10.1242/jcs.263408","DOIUrl":"10.1242/jcs.263408","url":null,"abstract":"The paradoxical exacerbation of cellular injury and death during reperfusion remains a problem in the treatment of myocardial infarction. Mitochondrial dysfunction plays a key role in the pathogenesis of myocardial ischemia and reperfusion injury. Dysfunctional mitochondria can be removed by mitophagy, culminating in their degradation within acidic lysosomes. Mitophagy is pivotal in maintaining cardiac homeostasis and emerges as a potential therapeutic target. Here, we employed beating human engineered heart tissue (EHT) to assess mitochondrial dysfunction and mitophagy during ischemia and reperfusion simulation. Our data indicate adverse ultrastructural changes in mitochondrial morphology and impairment of mitochondrial respiration. Furthermore, our pH-sensitive mitophagy reporter EHTs, generated by a CRISPR/Cas9 endogenous knock-in strategy, revealed induced mitophagy flux in EHTs after ischemia and reperfusion simulation. The induced flux required the activity of the protein kinase ULK1, a member of the core autophagy machinery. Our results demonstrate the applicability of the reporter EHTs for mitophagy assessment in a clinically relevant setting. Deciphering mitophagy in the human heart will facilitate development of novel therapeutic strategies.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

NHR-85 modulates mitochondrial and lipid homeostasis to protect against α-synuclein aggregation in C. elegans. NHR-85调节线虫线粒体和脂质稳态以防止α-突触核蛋白聚集。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-01 Epub Date: 2025-05-09 DOI: 10.1242/jcs.263651

Dikaia Tsagkari, Maria Markaki, Nektarios Tavernarakis

{"title":"NHR-85 modulates mitochondrial and lipid homeostasis to protect against α-synuclein aggregation in C. elegans.","authors":"Dikaia Tsagkari, Maria Markaki, Nektarios Tavernarakis","doi":"10.1242/jcs.263651","DOIUrl":"https://doi.org/10.1242/jcs.263651","url":null,"abstract":"Peroxisome proliferator-activated receptors (PPARs), such as PPARδ, are transcription factors that play a pivotal role in energy and fat metabolism. PPARδ activates genes involved in lipid and glucose metabolism and is expressed in various human tissues, including all brain regions and especially neurons, where it regulates lipid homeostasis and contributes to neuroprotection. However, the precise molecular mechanisms underlying these protective effects remain poorly understood. Here, we identify the Caenorhabditis elegans nuclear hormone receptor NHR-85 as a putative orthologue of human PPARδ. Furthermore, we show that NHR-85 functions as an essential regulator of fat and energy metabolism, with significant impact on mitochondrial homeostasis, at least in part through modulation of mitophagy. Finally, we find that NHR-85 prevents α-synuclein aggregation in a nematode model of Parkinson's disease, suggesting that it might play a protective role in neurodegenerative diseases. Our results indicate that NHR-85 is a functional orthologue of PPARδ and support the use of C. elegans as a powerful in vivo model for dissecting PPARδ-related metabolic and neurodegenerative processes.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 9","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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