在复制衰老过程中,液泡pH值通过TORC1信号调节网格蛋白介导的内吞作用。

IF 6.4 1区 生物学 Q1 CELL BIOLOGY
Journal of Cell Biology Pub Date : 2025-11-03 Epub Date: 2025-09-24 DOI:10.1083/jcb.202412064
Kenneth Gabriel Antenor, Jaime Lee-Dadswell, Natasha Salahshour, Nina Grishchenko, Shaimaa Swaleh, Gurjyot Makhija, Allie Spangaro, Mojca Mattiazzi Usaj
{"title":"在复制衰老过程中,液泡pH值通过TORC1信号调节网格蛋白介导的内吞作用。","authors":"Kenneth Gabriel Antenor, Jaime Lee-Dadswell, Natasha Salahshour, Nina Grishchenko, Shaimaa Swaleh, Gurjyot Makhija, Allie Spangaro, Mojca Mattiazzi Usaj","doi":"10.1083/jcb.202412064","DOIUrl":null,"url":null,"abstract":"<p><p>Clathrin-mediated endocytosis (CME) is a critical cellular process that regulates nutrient uptake, membrane composition, and signaling. Although replicative aging affects many cellular functions, its impact on CME remains largely unknown. We show that in budding yeast, older cells have slower assembly of early and coat CME modules, resulting in longer endocytic turnover and reduced Mup1 internalization. This change in CME dynamics is mother cell-specific, and not observed in daughters. Our data also show that perturbing vacuolar pH, a key driver of aging phenotypes, in young cells mimics aging-like CME dynamics, while maintaining an acidic vacuolar pH in aging cells preserves CME dynamics typical of young cells. We demonstrate that the vacuolar pH effect on CME is regulated through TORC1 via the effector kinase Npr1. Finally, we show that rescuing CME in aging cells improves mitochondrial health. These findings reveal that age-associated changes in cellular and vacuolar pH impair CME, and suggest CME as a potential driver of early cellular aging.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 11","pages":""},"PeriodicalIF":6.4000,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Vacuolar pH regulates clathrin-mediated endocytosis through TORC1 signaling during replicative aging.\",\"authors\":\"Kenneth Gabriel Antenor, Jaime Lee-Dadswell, Natasha Salahshour, Nina Grishchenko, Shaimaa Swaleh, Gurjyot Makhija, Allie Spangaro, Mojca Mattiazzi Usaj\",\"doi\":\"10.1083/jcb.202412064\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Clathrin-mediated endocytosis (CME) is a critical cellular process that regulates nutrient uptake, membrane composition, and signaling. Although replicative aging affects many cellular functions, its impact on CME remains largely unknown. We show that in budding yeast, older cells have slower assembly of early and coat CME modules, resulting in longer endocytic turnover and reduced Mup1 internalization. This change in CME dynamics is mother cell-specific, and not observed in daughters. Our data also show that perturbing vacuolar pH, a key driver of aging phenotypes, in young cells mimics aging-like CME dynamics, while maintaining an acidic vacuolar pH in aging cells preserves CME dynamics typical of young cells. We demonstrate that the vacuolar pH effect on CME is regulated through TORC1 via the effector kinase Npr1. Finally, we show that rescuing CME in aging cells improves mitochondrial health. These findings reveal that age-associated changes in cellular and vacuolar pH impair CME, and suggest CME as a potential driver of early cellular aging.</p>\",\"PeriodicalId\":15211,\"journal\":{\"name\":\"Journal of Cell Biology\",\"volume\":\"224 11\",\"pages\":\"\"},\"PeriodicalIF\":6.4000,\"publicationDate\":\"2025-11-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Cell Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1083/jcb.202412064\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/9/24 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cell Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1083/jcb.202412064","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/9/24 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

网格蛋白介导的内吞作用(CME)是调节营养摄取、膜组成和信号传导的关键细胞过程。尽管复制衰老影响许多细胞功能,但其对CME的影响在很大程度上仍然未知。我们发现,在出芽酵母中,较老的细胞较慢地组装早期和外壳CME模块,导致更长的内噬周转和减少Mup1内化。CME动力学的这种变化是母细胞特异性的,在子细胞中未观察到。我们的数据还表明,在年轻细胞中,扰动液泡pH值(衰老表型的关键驱动因素)模拟了衰老样CME动力学,而在衰老细胞中维持酸性液泡pH值则保留了年轻细胞典型的CME动力学。我们证明液泡pH对CME的影响是通过效应激酶Npr1通过TORC1调节的。最后,我们表明,挽救衰老细胞中的CME可改善线粒体健康。这些发现表明,细胞和液泡pH值的年龄相关变化会损害CME,并提示CME是早期细胞衰老的潜在驱动因素。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Vacuolar pH regulates clathrin-mediated endocytosis through TORC1 signaling during replicative aging.

Clathrin-mediated endocytosis (CME) is a critical cellular process that regulates nutrient uptake, membrane composition, and signaling. Although replicative aging affects many cellular functions, its impact on CME remains largely unknown. We show that in budding yeast, older cells have slower assembly of early and coat CME modules, resulting in longer endocytic turnover and reduced Mup1 internalization. This change in CME dynamics is mother cell-specific, and not observed in daughters. Our data also show that perturbing vacuolar pH, a key driver of aging phenotypes, in young cells mimics aging-like CME dynamics, while maintaining an acidic vacuolar pH in aging cells preserves CME dynamics typical of young cells. We demonstrate that the vacuolar pH effect on CME is regulated through TORC1 via the effector kinase Npr1. Finally, we show that rescuing CME in aging cells improves mitochondrial health. These findings reveal that age-associated changes in cellular and vacuolar pH impair CME, and suggest CME as a potential driver of early cellular aging.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of Cell Biology
Journal of Cell Biology 生物-细胞生物学
CiteScore
12.60
自引率
2.60%
发文量
213
审稿时长
1 months
期刊介绍: The Journal of Cell Biology (JCB) is a comprehensive journal dedicated to publishing original discoveries across all realms of cell biology. We invite papers presenting novel cellular or molecular advancements in various domains of basic cell biology, along with applied cell biology research in diverse systems such as immunology, neurobiology, metabolism, virology, developmental biology, and plant biology. We enthusiastically welcome submissions showcasing significant findings of interest to cell biologists, irrespective of the experimental approach.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信