Pub Date : 2026-02-02Epub Date: 2025-12-29DOI: 10.1083/jcb.202511183
Michael J Clague
In this issue, Xiong et al. (https://doi.org/10.1083/jcb.202503169) introduce mouse models that enable tissue-resolved mapping of peroxisome turnover and pexophagy across development, metabolism, and disease. This study reveals striking cell type-specific differences in peroxisome dynamics and establishes a versatile platform for dissecting how pexophagy integrates with mitochondrial quality control and whole-body metabolic homeostasis.
{"title":"Pexophagy meets physiology.","authors":"Michael J Clague","doi":"10.1083/jcb.202511183","DOIUrl":"https://doi.org/10.1083/jcb.202511183","url":null,"abstract":"<p><p>In this issue, Xiong et al. (https://doi.org/10.1083/jcb.202503169) introduce mouse models that enable tissue-resolved mapping of peroxisome turnover and pexophagy across development, metabolism, and disease. This study reveals striking cell type-specific differences in peroxisome dynamics and establishes a versatile platform for dissecting how pexophagy integrates with mitochondrial quality control and whole-body metabolic homeostasis.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 2","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878436","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}
Most animal cells display widespread plasma membrane (PM) folding. It is unclear how cortical tension is generated and controlled over cell surfaces with such PM topography. Our results highlight the early syncytial Drosophila embryo as a model of cortical actomyosin network integration with complex PM topography. Over the embryo surface, before arrival of peripheral nuclei, actomyosin networks entwine across a dense field of PM infoldings. Actomyosin network and PM topography changes are closely coupled during synchronous mitotic cycles and following experimental perturbations. Actomyosin activity is required for periods of condensed spacing between PM infoldings, when the integration of actomyosin networks and PM topography seems to form a tensile, composite material. These cyclic condensations are preceded by periods of expanded spacing between PM infoldings driven by Arp2/3 activity. Without Arp2/3 activity, the actomyosin cortex and PM topography gain an aberrant configuration, excessive tension is evident, and embryo surface distortions occur. Overall, PM topography seems integral to actomyosin cortex function and regulation.
{"title":"Actomyosin cortex integration with complex plasma membrane topography in the early Drosophila embryo.","authors":"Rowan K Naidoo,Rebecca Tam,Tony J C Harris","doi":"10.1083/jcb.202509151","DOIUrl":"https://doi.org/10.1083/jcb.202509151","url":null,"abstract":"Most animal cells display widespread plasma membrane (PM) folding. It is unclear how cortical tension is generated and controlled over cell surfaces with such PM topography. Our results highlight the early syncytial Drosophila embryo as a model of cortical actomyosin network integration with complex PM topography. Over the embryo surface, before arrival of peripheral nuclei, actomyosin networks entwine across a dense field of PM infoldings. Actomyosin network and PM topography changes are closely coupled during synchronous mitotic cycles and following experimental perturbations. Actomyosin activity is required for periods of condensed spacing between PM infoldings, when the integration of actomyosin networks and PM topography seems to form a tensile, composite material. These cyclic condensations are preceded by periods of expanded spacing between PM infoldings driven by Arp2/3 activity. Without Arp2/3 activity, the actomyosin cortex and PM topography gain an aberrant configuration, excessive tension is evident, and embryo surface distortions occur. Overall, PM topography seems integral to actomyosin cortex function and regulation.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"34 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073087","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}
Jill E Falk,Tobias Henke,Sindhuja Gowrisankaran,Simone Wanderoy,Himanish Basu,Sinead Greally,Judith Steen,Thomas L Schwarz
Neuronal signaling requires large amounts of ATP, making neurons particularly sensitive to defects in energy homeostasis. Mitochondrial movement and energy production are therefore regulated to align local demands with mitochondrial output. Here, we report a pathway that arrests mitochondria in response to decreases in the ATP-to-AMP ratio, an indication that ATP consumption exceeds supply. In neurons and cell lines, low concentrations of the electron transport chain inhibitor antimycin A decrease the production of ATP and concomitantly arrest mitochondrial movement without triggering mitophagy. This arrest is accompanied by the accumulation of actin fibers adjacent to the mitochondria, which serve as an anchor that resists the associated motors. This arrest is mediated by activation of the energy-sensing kinase AMPK, which phosphorylates TRAK1. This mechanism likely helps maintain cellular energy homeostasis by anchoring energy-producing mitochondria in places where they are most needed.
{"title":"Energy stress activates AMPK to arrest mitochondria via phosphorylation of TRAK1.","authors":"Jill E Falk,Tobias Henke,Sindhuja Gowrisankaran,Simone Wanderoy,Himanish Basu,Sinead Greally,Judith Steen,Thomas L Schwarz","doi":"10.1083/jcb.202501023","DOIUrl":"https://doi.org/10.1083/jcb.202501023","url":null,"abstract":"Neuronal signaling requires large amounts of ATP, making neurons particularly sensitive to defects in energy homeostasis. Mitochondrial movement and energy production are therefore regulated to align local demands with mitochondrial output. Here, we report a pathway that arrests mitochondria in response to decreases in the ATP-to-AMP ratio, an indication that ATP consumption exceeds supply. In neurons and cell lines, low concentrations of the electron transport chain inhibitor antimycin A decrease the production of ATP and concomitantly arrest mitochondrial movement without triggering mitophagy. This arrest is accompanied by the accumulation of actin fibers adjacent to the mitochondria, which serve as an anchor that resists the associated motors. This arrest is mediated by activation of the energy-sensing kinase AMPK, which phosphorylates TRAK1. This mechanism likely helps maintain cellular energy homeostasis by anchoring energy-producing mitochondria in places where they are most needed.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"117 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073026","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}
During embryogenesis, dynamic changes in tissue architecture transform primitive anlages to functional organs. Using a new apical-polarity mouse reporter, we document in real time how the pancreatic ductal system is derived and transformed, revealing that dynamic remodeling of apical proteins and lumens primarily drive each stage. Contrary to current "de novo" models of polarity acquisition, we show that expansion and rearrangement of the preexisting central primary lumen drives early pancreatic ductal network establishment. The resulting ductal plexus creates unique ECM rich niches for endocrinogenesis, which are subsequently remodeled into an arborized system by a new mechanism, which we term "loop closing." We furthermore demonstrate that inner lumenal rearrangements precede outer epithelial branching. These novel tissue dynamics provide a new framework within which cell and molecular signaling can be investigated to better understand the interplay between organ architecture and cell fate.
{"title":"Real-time imaging reveals new mechanisms for pancreatic ductal establishment and remodeling.","authors":"Abigail Laura Jackson,Silja Heilmann,Rikke Agerskov,Christine Ebeid,Jelena Miskovic Krivokapic,Jose Alejandro Romero Herrera,Henrik Semb,Pia Nyeng","doi":"10.1083/jcb.202409022","DOIUrl":"https://doi.org/10.1083/jcb.202409022","url":null,"abstract":"During embryogenesis, dynamic changes in tissue architecture transform primitive anlages to functional organs. Using a new apical-polarity mouse reporter, we document in real time how the pancreatic ductal system is derived and transformed, revealing that dynamic remodeling of apical proteins and lumens primarily drive each stage. Contrary to current \"de novo\" models of polarity acquisition, we show that expansion and rearrangement of the preexisting central primary lumen drives early pancreatic ductal network establishment. The resulting ductal plexus creates unique ECM rich niches for endocrinogenesis, which are subsequently remodeled into an arborized system by a new mechanism, which we term \"loop closing.\" We furthermore demonstrate that inner lumenal rearrangements precede outer epithelial branching. These novel tissue dynamics provide a new framework within which cell and molecular signaling can be investigated to better understand the interplay between organ architecture and cell fate.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"293 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056911","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}
The cyclin-dependent kinase subunit CKS remains poorly understood. We found that Caenorhabditis elegans CKS-1 and its partner CDK-1 co-localized to the cytosol, chromosomes, and spindle structures throughout cell division. Nevertheless, CKS-1 was required well after CDK-1, during oocyte meiosis I metaphase, which was prolonged in cks-1 mutants. Anaphase A precedes anaphase B in C. elegans oocytes, and while delayed in onset, chromosomes in cks-1 mutants separated normally during meiosis I anaphase A but failed to separate further and instead rapidly transitioned into meiosis II prometaphase, skipping anaphase B. The anaphase A to B transition also was defective during meiosis II. Furthermore, meiosis I anaphase B required that CKS-1 be bound to CDK-1 and have a functional anion pocket. Finally, our results suggest that CKS-1 promotes anaphase onset during meiosis I through securin destruction and during meiosis II through cyclin B1 destruction, and that both securin and cyclin B3 have positive roles independent of their destruction during meiosis II.
{"title":"Anaphase onset requires CKS-1-mediated destruction of securin in meiosis I and cyclin B1 in meiosis II.","authors":"Jie Yang,Eisuke Sumiyoshi,Bruce Bowerman","doi":"10.1083/jcb.202502087","DOIUrl":"https://doi.org/10.1083/jcb.202502087","url":null,"abstract":"The cyclin-dependent kinase subunit CKS remains poorly understood. We found that Caenorhabditis elegans CKS-1 and its partner CDK-1 co-localized to the cytosol, chromosomes, and spindle structures throughout cell division. Nevertheless, CKS-1 was required well after CDK-1, during oocyte meiosis I metaphase, which was prolonged in cks-1 mutants. Anaphase A precedes anaphase B in C. elegans oocytes, and while delayed in onset, chromosomes in cks-1 mutants separated normally during meiosis I anaphase A but failed to separate further and instead rapidly transitioned into meiosis II prometaphase, skipping anaphase B. The anaphase A to B transition also was defective during meiosis II. Furthermore, meiosis I anaphase B required that CKS-1 be bound to CDK-1 and have a functional anion pocket. Finally, our results suggest that CKS-1 promotes anaphase onset during meiosis I through securin destruction and during meiosis II through cyclin B1 destruction, and that both securin and cyclin B3 have positive roles independent of their destruction during meiosis II.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"16 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015262","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}
Meiotic progression requires the activity of the cyclin B-CDK1 complex. In this issue, Yang et al. (https://doi.org/10.1083/jcb.202502087) demonstrate that the phospho-adaptor protein CKS-1 functions as a critical component of this complex to ensure proper chromosome segregation during oocyte meiosis.
{"title":"CKS-1 and the choreography of meiotic chromosome segregation.","authors":"Shabnam Moghareh,David Bojorquez,Pablo Lara-Gonzalez","doi":"10.1083/jcb.202511196","DOIUrl":"https://doi.org/10.1083/jcb.202511196","url":null,"abstract":"Meiotic progression requires the activity of the cyclin B-CDK1 complex. In this issue, Yang et al. (https://doi.org/10.1083/jcb.202502087) demonstrate that the phospho-adaptor protein CKS-1 functions as a critical component of this complex to ensure proper chromosome segregation during oocyte meiosis.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"192 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015263","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}
Collective cell migration is essential for development and tissue homeostasis and plays a central role in pathological processes such as tumor metastasis. While extensively studied in epithelial cells, collective migration is also observed in mesenchymal cells, though the mechanistic similarities and differences between these modes remain unclear. Here, we use neural crest (NC) cells to investigate collective chemotaxis in epithelial and mesenchymal states within the same lineage. Mesenchymal NC clusters migrate collectively toward the chemoattractant SDF-1 through rear-directed contractility of supracellular actomyosin cables and polarized front-edge protrusions. In contrast, epithelial NC cells exhibit polarized cryptic protrusions and increased active Rac1 localization at E-cadherin-mediated junctions. During epithelial chemotaxis, traction forces originate from internal cell-cell junctions, whereas in mesenchymal clusters, they remain peripheral. Our findings reveal that mesenchymal collective chemotaxis relies on supracellular force coordination, while epithelial chemotaxis depends on force generation by individual cells within the collective.
{"title":"Force coordination distinguishes epithelial and mesenchymal modes of collective chemotaxis.","authors":"Jorge Diaz,Roberto Mayor","doi":"10.1083/jcb.202507211","DOIUrl":"https://doi.org/10.1083/jcb.202507211","url":null,"abstract":"Collective cell migration is essential for development and tissue homeostasis and plays a central role in pathological processes such as tumor metastasis. While extensively studied in epithelial cells, collective migration is also observed in mesenchymal cells, though the mechanistic similarities and differences between these modes remain unclear. Here, we use neural crest (NC) cells to investigate collective chemotaxis in epithelial and mesenchymal states within the same lineage. Mesenchymal NC clusters migrate collectively toward the chemoattractant SDF-1 through rear-directed contractility of supracellular actomyosin cables and polarized front-edge protrusions. In contrast, epithelial NC cells exhibit polarized cryptic protrusions and increased active Rac1 localization at E-cadherin-mediated junctions. During epithelial chemotaxis, traction forces originate from internal cell-cell junctions, whereas in mesenchymal clusters, they remain peripheral. Our findings reveal that mesenchymal collective chemotaxis relies on supracellular force coordination, while epithelial chemotaxis depends on force generation by individual cells within the collective.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"26 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005342","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}
Emily D Fabiano,Elle P Techasiriwan,Lindsey N Sabo,Nathaniel Seluga,Brenton D Hoffman,Cynthia A Reinhart-King
Cell migration and cytoskeletal remodeling are energetically demanding processes. Reorganizing the cytoskeleton requires ATP to fuel the actomyosin complex, enabling cells to adhere to and migrate through a matrix. While it is known that energy is required for cell migration, the mechanism by which cell-extracellular matrix adhesion influences cell energetics is unclear. Here, we investigated the relationship between cell-extracellular matrix adhesion and cellular metabolic state with a focus on vinculin given its role in connecting the cytoskeleton to focal adhesions and extracellular space. Knocking out vinculin increases the metabolic activity in cells and results in fast, frequent Rho kinase activity-dependent changes in cell shape and protrusions. The cellular protrusion dynamics and bioenergetics are interrelated processes, as stimulating RhoA/Rho kinase activity increases dynamic blebbing protrusions and energy production, and inhibiting metabolism decreases the frequency of blebbing cell protrusions. This link between cell-extracellular matrix adhesion and bioenergetics provides a novel basis by which cellular metabolism and cell migration could be controlled.
{"title":"Mechanometabolism of cell adhesion: Vinculin regulates bioenergetics via RhoA-ROCK.","authors":"Emily D Fabiano,Elle P Techasiriwan,Lindsey N Sabo,Nathaniel Seluga,Brenton D Hoffman,Cynthia A Reinhart-King","doi":"10.1083/jcb.202504025","DOIUrl":"https://doi.org/10.1083/jcb.202504025","url":null,"abstract":"Cell migration and cytoskeletal remodeling are energetically demanding processes. Reorganizing the cytoskeleton requires ATP to fuel the actomyosin complex, enabling cells to adhere to and migrate through a matrix. While it is known that energy is required for cell migration, the mechanism by which cell-extracellular matrix adhesion influences cell energetics is unclear. Here, we investigated the relationship between cell-extracellular matrix adhesion and cellular metabolic state with a focus on vinculin given its role in connecting the cytoskeleton to focal adhesions and extracellular space. Knocking out vinculin increases the metabolic activity in cells and results in fast, frequent Rho kinase activity-dependent changes in cell shape and protrusions. The cellular protrusion dynamics and bioenergetics are interrelated processes, as stimulating RhoA/Rho kinase activity increases dynamic blebbing protrusions and energy production, and inhibiting metabolism decreases the frequency of blebbing cell protrusions. This link between cell-extracellular matrix adhesion and bioenergetics provides a novel basis by which cellular metabolism and cell migration could be controlled.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"6 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005481","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}
The endosomal sorting complex required for transport III (ESCRT-III) is conserved machinery that drives membrane abscission. While ESCRT-III flat spirals are proposed as a primed state, their essential role and regulation remain unclear. Leveraging our newly resolved architecture of yeast Snf7 flat spirals, we engineered a series of Snf7 mutants by inserting polyglycines into the linker between the helices α4 and α5. Our results demonstrate that extending the linker can transform Snf7 flat spirals into rings. Cryogenic electron microscopy analyses of these Snf7 rings reveal that the linker extension specifically relaxes α2/3 into a bent conformation while leaving other regions of Snf7 unaffected. Importantly, Snf7 rings are unable to mediate membrane abscission to form intraluminal vesicles, resulting in pronounced yeast sensitivity to extracellular canavanine. Our work identifies the linker as a critical regulator of ESCRT-III spiral assembly and establishes flat spirals as indispensable for membrane abscission, offering fundamental molecular insights into the membrane abscission mediated by ESCRT-III flat spirals.
{"title":"Linker extension impairs ESCRT-III flat spirals and the mediated membrane abscission.","authors":"Mingdong Liu,Liuyan Yang,Rong Huang,Lei Qi,Tiefeng Song,Yuxuan Huang,Yunhui Liu,Yu-Zhong Zhang,Yong Wang,Qing-Tao Shen","doi":"10.1083/jcb.202503160","DOIUrl":"https://doi.org/10.1083/jcb.202503160","url":null,"abstract":"The endosomal sorting complex required for transport III (ESCRT-III) is conserved machinery that drives membrane abscission. While ESCRT-III flat spirals are proposed as a primed state, their essential role and regulation remain unclear. Leveraging our newly resolved architecture of yeast Snf7 flat spirals, we engineered a series of Snf7 mutants by inserting polyglycines into the linker between the helices α4 and α5. Our results demonstrate that extending the linker can transform Snf7 flat spirals into rings. Cryogenic electron microscopy analyses of these Snf7 rings reveal that the linker extension specifically relaxes α2/3 into a bent conformation while leaving other regions of Snf7 unaffected. Importantly, Snf7 rings are unable to mediate membrane abscission to form intraluminal vesicles, resulting in pronounced yeast sensitivity to extracellular canavanine. Our work identifies the linker as a critical regulator of ESCRT-III spiral assembly and establishes flat spirals as indispensable for membrane abscission, offering fundamental molecular insights into the membrane abscission mediated by ESCRT-III flat spirals.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"6 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005345","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}
Adam James Waite,Beiduo Rao,Elizabeth Schinski,Nathaniel H Thayer,Manuel Hotz,Austin E Y T Lefebvre,Celeste Sandoval,Daniel E Gottschling
Age-associated decline in mitochondrial membrane potential (MMP) is a ubiquitous aspect of eukaryotic organisms and is associated with many aging-related diseases. However, it is not clear whether this decline is a cause or consequence of aging, and therefore whether interventions to reduce MMP decline are a viable strategy to promote healthier aging and longer lifespans. We developed a screening platform in Saccharomyces cerevisiae to identify mutations that slowed or abrogated the age-associated decline in MMP. Characterization of the longest-lived mutant revealed that reduced internal potassium increased MMP and extended lifespan. Distinct interventions improved cellular MMP and lifespan: deleting a potassium transporter; altering the balance between kinases and phosphatases that control potassium transporter activity; and reducing available potassium in the environment. Similarly, in isolated mitochondria, reducing the concentration of potassium was sufficient to increase MMP. These data indicate that the most abundant monovalent cation in eukaryotic cells plays a critical role in tuning mitochondrial function, consequently impacting lifespan.
{"title":"Potassium ion homeostasis modulates mitochondrial function.","authors":"Adam James Waite,Beiduo Rao,Elizabeth Schinski,Nathaniel H Thayer,Manuel Hotz,Austin E Y T Lefebvre,Celeste Sandoval,Daniel E Gottschling","doi":"10.1083/jcb.202505110","DOIUrl":"https://doi.org/10.1083/jcb.202505110","url":null,"abstract":"Age-associated decline in mitochondrial membrane potential (MMP) is a ubiquitous aspect of eukaryotic organisms and is associated with many aging-related diseases. However, it is not clear whether this decline is a cause or consequence of aging, and therefore whether interventions to reduce MMP decline are a viable strategy to promote healthier aging and longer lifespans. We developed a screening platform in Saccharomyces cerevisiae to identify mutations that slowed or abrogated the age-associated decline in MMP. Characterization of the longest-lived mutant revealed that reduced internal potassium increased MMP and extended lifespan. Distinct interventions improved cellular MMP and lifespan: deleting a potassium transporter; altering the balance between kinases and phosphatases that control potassium transporter activity; and reducing available potassium in the environment. Similarly, in isolated mitochondria, reducing the concentration of potassium was sufficient to increase MMP. These data indicate that the most abundant monovalent cation in eukaryotic cells plays a critical role in tuning mitochondrial function, consequently impacting lifespan.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"49 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956190","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}
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