Journal of cell science最新文献

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

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

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

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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondria-plasma membrane contact sites regulate the ER-mitochondria encounter structure. 线粒体-质膜接触位点调节er -线粒体相遇结构。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-01 Epub Date: 2025-02-18 DOI: 10.1242/jcs.263685

Jason C Casler, Clare S Harper, Laura L Lackner

{"title":"Mitochondria-plasma membrane contact sites regulate the ER-mitochondria encounter structure.","authors":"Jason C Casler, Clare S Harper, Laura L Lackner","doi":"10.1242/jcs.263685","DOIUrl":"10.1242/jcs.263685","url":null,"abstract":"Cells form multiple, molecularly distinct membrane contact sites (MCSs) between organelles. Despite knowing the molecular identity of several of these complexes, little is known about how MCSs are coordinately regulated in space and time to promote organelle function. Here, we examined two well-characterized mitochondria-endoplasmic reticulum (ER) MCSs - the ER-mitochondria encounter structure (ERMES) and the mitochondria-ER-cortex anchor (MECA) in Saccharomyces cerevisiae. We report that loss of MECA results in a substantial reduction in the number of ERMES contacts. Rather than reducing ERMES protein levels, loss of MECA results in an increase in the size of ERMES contacts. Using live-cell microscopy, we demonstrate that ERMES contacts display several dynamic behaviors, such as de novo formation, fusion and fission, that are altered in the absence of MECA or by changes in growth conditions. Unexpectedly, we find that the mitochondria-plasma membrane (PM) tethering, and not the mitochondria-ER tethering, function of MECA regulates ERMES contacts. Remarkably, synthetic tethering of mitochondria to the PM in the absence of MECA is sufficient to rescue the distribution of ERMES foci. Overall, our work reveals how one MCS can influence the regulation and function of another.","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/PMC11883241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059232","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

ER-mitochondria encounter structure connections determine drug sensitivity and virulence of Cryptococcus neoformans. er -线粒体相遇结构连接决定了新型隐球菌的药物敏感性和毒力。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-01 Epub Date: 2025-04-03 DOI: 10.1242/jcs.263558

Deepika Kumari, Mohit Kumar, Naseem A Gaur, Lucky Duhan, Nadezhda Sachivkina, Raman Manoharlal, Ritu Pasrija

{"title":"ER-mitochondria encounter structure connections determine drug sensitivity and virulence of Cryptococcus neoformans.","authors":"Deepika Kumari, Mohit Kumar, Naseem A Gaur, Lucky Duhan, Nadezhda Sachivkina, Raman Manoharlal, Ritu Pasrija","doi":"10.1242/jcs.263558","DOIUrl":"10.1242/jcs.263558","url":null,"abstract":"Cryptococcus neoformans is a common fungal pathogen, causing fatal meningoencephalitis in immunocompromised individuals. The limited availability of antifungals and increasing resistance in pathogens including C. neoformans emphasize the need to find new drugs. Mitochondria have long been associated with drug resistance in fungi. They are connected to the endoplasmic reticulum (ER) via a multiprotein complex, the ER-mitochondria encounter structure (ERMES), which is unique in the fungal kingdom. In this study on C. neoformans, the four subunits of the ERMES complex, namely, Mmm1, Mdm12, Mdm10 and Mdm34, were deleted to generate the strains Δmmm1, Δmdm12, Δmdm10 and Δmdm34, respectively. These mutants had impaired mitochondria and were sensitive to antifungals, including echinocandins, due to lower chitin content. Virulence factors, including capsule formation and melanin production, were debilitated in the mutants. The partner organelle ER was also affected by compromised ERMES contact, as the activity of several ER-synthesized enzymes involved in virulence was impacted. The in vivo studies in Caenorhabditis elegans model of cryptococcosis confirmed the reduced virulence of the mutants. These results indicate that the impairment of the ERMES complex is crucial for the virulence and pathogenesis of C. neoformans.","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":"143772536","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

Mitochondrial fission - changing perspectives for future progress. 线粒体裂变——改变未来进展的前景。

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.263640

Sukrut C Kamerkar, Ao Liu, Henry N Higgs

{"title":"Mitochondrial fission - changing perspectives for future progress.","authors":"Sukrut C Kamerkar, Ao Liu, Henry N Higgs","doi":"10.1242/jcs.263640","DOIUrl":"https://doi.org/10.1242/jcs.263640","url":null,"abstract":"Mitochondrial fission is important for many aspects of cellular homeostasis, including mitochondrial distribution, stress response, mitophagy, mitochondrially derived vesicle production and metabolic regulation. Several decades of research has revealed much about fission, including identification of a key division protein - the dynamin Drp1 (also known as DNM1L) - receptors for Drp1 on the outer mitochondrial membrane (OMM), including Mff, MiD49 and MiD51 (also known as MIEF2 and MIEF1, respectively) and Fis1, and important Drp1 regulators, including post-translational modifications, actin filaments and the phospholipid cardiolipin. In addition, it is now appreciated that other organelles, including the endoplasmic reticulum, lysosomes and Golgi-derived vesicles, can participate in mitochondrial fission. However, a more holistic understanding of the process is lacking. In this Review, we address three questions that highlight knowledge gaps. First, how do we quantify mitochondrial fission? Second, how does the inner mitochondrial membrane (IMM) divide? Third, how many 'types' of fission exist? We also introduce a model that integrates multiple regulatory factors in mammalian mitochondrial fission. In this model, three possible pathways (cellular stimulation, metabolic switching or mitochondrial dysfunction) independently initiate Drp1 recruitment at the fission site, followed by a shared second step in which Mff mediates subsequent assembly of a contractile Drp1 ring. We conclude by discussing some perplexing issues in fission regulation, including the effects of Drp1 phosphorylation and the multiple Drp1 isoforms.","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":"143657032","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

Fis1 regulates mitochondrial morphology, bioenergetics and removal of mitochondrial DNA damage in irradiated glioblastoma cells. Fis1调节辐照胶质母细胞瘤细胞的线粒体形态、生物能量学和mtDNA损伤的去除。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-01 Epub Date: 2025-01-28 DOI: 10.1242/jcs.263459

Yuli Buckley, Maria S K Stoll, Charles L Hoppel, Jason A Mears

{"title":"Fis1 regulates mitochondrial morphology, bioenergetics and removal of mitochondrial DNA damage in irradiated glioblastoma cells.","authors":"Yuli Buckley, Maria S K Stoll, Charles L Hoppel, Jason A Mears","doi":"10.1242/jcs.263459","DOIUrl":"10.1242/jcs.263459","url":null,"abstract":"In response to external stress, mitochondrial dynamics is often disrupted, but the associated physiologic changes are often uncharacterized. In many cancers, including glioblastoma (GBM), mitochondrial dysfunction has been observed. Understanding how mitochondrial dynamics and physiology contribute to treatment resistance will lead to more targeted and effective therapeutics. This study aims to uncover how mitochondria in GBM cells adapt to and resist ionizing radiation (IR), a component of the standard of care for GBM. Using several approaches, we investigated how mitochondrial dynamics and physiology adapt to radiation stress, and we uncover a novel role for Fis1, a pro-fission protein, in regulating the stress response through mitochondrial DNA (mtDNA) maintenance and altered mitochondrial bioenergetics. Importantly, our data demonstrate that increased fission in response to IR leads to removal of mtDNA damage and more efficient oxygen consumption through altered electron transport chain (ETC) activities in intact mitochondria. These findings demonstrate a key role for Fis1 in targeting damaged mtDNA for degradation and regulating mitochondrial bioenergetics through altered dynamics.","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/PMC11828467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864233","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

Tumor acidosis supports cancer cell lipid uptake via a rapid, transporter-independent mechanism. 肿瘤酸中毒通过一种快速的、不依赖于转运蛋白的机制支持癌细胞脂质摄取。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-04-07 DOI: 10.1242/jcs.263688

Marc Severin, Rikke K Hansen, Michala G Rolver, Tove Hels, Kenji Maeda, Luis A Pardo, Stine F Pedersen

{"title":"Tumor acidosis supports cancer cell lipid uptake via a rapid, transporter-independent mechanism.","authors":"Marc Severin, Rikke K Hansen, Michala G Rolver, Tove Hels, Kenji Maeda, Luis A Pardo, Stine F Pedersen","doi":"10.1242/jcs.263688","DOIUrl":"https://doi.org/10.1242/jcs.263688","url":null,"abstract":"Tumor acidosis alters cancer cell metabolism and favors aggressive disease progression. Cancer cells in acidic environments increase lipid droplet (LD) accumulation and oxidative phosphorylation, characteristics of aggressive cancers. Here, we use live imaging, shotgun lipidomics, and immunofluorescence analyses of mammary and pancreatic cancer cells to demonstrate that both acute acidosis and adaptation to acidic growth drive rapid uptake of fatty acids (FA), which are converted to triacylglycerols (TAG) and stored in LDs. Consistent with its independence of de novo synthesis, TAG- and LD accumulation in acid-adapted cells is unaffected by FA-synthetase inhibitors. Macropinocytosis, which is upregulated in acid-adapted cells, partially contributes to FA uptake, which is independent of other protein-facilitated lipid uptake mechanisms, including CD36, FATP2, and caveolin- and clathrin-dependent endocytosis. We propose that a major mechanism by which tumor acidosis drives FA uptake is through neutralizing protonation of negatively charged FAs allowing their diffusive, transporter-independent uptake. We suggest that this could be a major factor triggering acidosis-driven metabolic rewiring.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795577","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

Cell deformations generated by stochastic actomyosin waves drive in vivo random-walk swimming migration. 随机肌动蛋白波产生的细胞变形驱动体内随机游动迁移。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-04-04 DOI: 10.1242/jcs.263787

Cyril Andrieu, Bren Hunyi Lee, Anna Franz

{"title":"Cell deformations generated by stochastic actomyosin waves drive in vivo random-walk swimming migration.","authors":"Cyril Andrieu, Bren Hunyi Lee, Anna Franz","doi":"10.1242/jcs.263787","DOIUrl":"https://doi.org/10.1242/jcs.263787","url":null,"abstract":"Amoeboid cell migration drives many developmental and disease-related processes including immune responses and cancer metastasis. Swimming migration is a subtype of amoeboid migration observed in cells in suspension ex vivo. However, the mechanism underlying swimming migration in vivo is unknown. Using Drosophila fat body cells (FBCs) as a model, we show that FBCs actively swim to patrol the pupa by random-walk. Their migration is powered through actomyosin waves, that exert compressive forces as they travel to the cell rear causing cell deformations. Unlike in other types of amoeboid migration, RhoA, Cdc42 and Rac1, are all required for FBC migration to regulate formin-driven actin polymerisation. We find that RhoA at the cell rear induces actomyosin contractions via Rho kinase and myosin II. We show that contractile actin waves display a stochastic behaviour, inducing either cell elongation or rounding, suggesting that nonreciprocal cell deformations drive locomotion. Importantly, our work in a physiological system reveals that stochastic actomyosin waves promote random-walk swimming migration to enable fast, long-range cell dispersal. We propose that this individualist migration behaviour collectively allows patrolling of the pupal body.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780097","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