Lactylation stabilizes TFEB to elevate autophagy and lysosomal activity.

IF 7.4 1区 生物学 Q1 CELL BIOLOGY Journal of Cell Biology Pub Date : 2024-11-04 Epub Date: 2024-08-28 DOI:10.1083/jcb.202308099
Yewei Huang, Gan Luo, Kesong Peng, Yue Song, Yusha Wang, Hongtao Zhang, Jin Li, Xiangmin Qiu, Maomao Pu, Xinchang Liu, Chao Peng, Dante Neculai, Qiming Sun, Tianhua Zhou, Pintong Huang, Wei Liu
{"title":"Lactylation stabilizes TFEB to elevate autophagy and lysosomal activity.","authors":"Yewei Huang, Gan Luo, Kesong Peng, Yue Song, Yusha Wang, Hongtao Zhang, Jin Li, Xiangmin Qiu, Maomao Pu, Xinchang Liu, Chao Peng, Dante Neculai, Qiming Sun, Tianhua Zhou, Pintong Huang, Wei Liu","doi":"10.1083/jcb.202308099","DOIUrl":null,"url":null,"abstract":"<p><p>The transcription factor TFEB is a major regulator of lysosomal biogenesis and autophagy. There is growing evidence that posttranslational modifications play a crucial role in regulating TFEB activity. Here, we show that lactate molecules can covalently modify TFEB, leading to its lactylation and stabilization. Mechanically, lactylation at K91 prevents TFEB from interacting with E3 ubiquitin ligase WWP2, thereby inhibiting TFEB ubiquitination and proteasome degradation, resulting in increased TFEB activity and autophagy flux. Using a specific antibody against lactylated K91, enhanced TFEB lactylation was observed in clinical human pancreatic cancer samples. Our results suggest that lactylation is a novel mode of TFEB regulation and that lactylation of TFEB may be associated with high levels of autophagy in rapidly proliferating cells, such as cancer cells.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":null,"pages":null},"PeriodicalIF":7.4000,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11354204/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cell Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1083/jcb.202308099","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/28 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

The transcription factor TFEB is a major regulator of lysosomal biogenesis and autophagy. There is growing evidence that posttranslational modifications play a crucial role in regulating TFEB activity. Here, we show that lactate molecules can covalently modify TFEB, leading to its lactylation and stabilization. Mechanically, lactylation at K91 prevents TFEB from interacting with E3 ubiquitin ligase WWP2, thereby inhibiting TFEB ubiquitination and proteasome degradation, resulting in increased TFEB activity and autophagy flux. Using a specific antibody against lactylated K91, enhanced TFEB lactylation was observed in clinical human pancreatic cancer samples. Our results suggest that lactylation is a novel mode of TFEB regulation and that lactylation of TFEB may be associated with high levels of autophagy in rapidly proliferating cells, such as cancer cells.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
乳化作用可稳定 TFEB,从而提高自噬和溶酶体活性。
转录因子 TFEB 是溶酶体生物发生和自噬的主要调节因子。越来越多的证据表明,翻译后修饰在调节 TFEB 活性方面发挥着至关重要的作用。在这里,我们发现乳酸分子可以对 TFEB 进行共价修饰,导致其乳化和稳定。从机理上讲,K91处的乳化可阻止TFEB与E3泛素连接酶WWP2相互作用,从而抑制TFEB的泛素化和蛋白酶体降解,导致TFEB活性和自噬通量增加。利用针对乳化 K91 的特异性抗体,在临床人类胰腺癌样本中观察到了增强的 TFEB 乳化作用。我们的研究结果表明,乳化是一种新型的 TFEB 调节模式,TFEB 的乳化可能与快速增殖细胞(如癌细胞)的高水平自噬有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 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.
期刊最新文献
Arrayed CRISPRi library to suppress genes required for Schizosaccharomyces pombe viability. Postsynaptic BMP signaling regulates myonuclear properties in Drosophila larval muscles. Heterogeneity of late endosome/lysosomes shown by multiplexed DNA-PAINT imaging. Kinetochores grip microtubules with directionally asymmetric strength. Definition of phosphatidylinositol 4,5-bisphosphate distribution by freeze-fracture replica labeling.
×
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
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 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 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1