Lactylation stabilizes TFEB to elevate autophagy and lysosomal activity.

Autor:	Huang Y; Center for Metabolism Research, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University , Yiwu, China., Luo G; Center for Metabolism Research, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University , Yiwu, China., Peng K; Center for Metabolism Research, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University , Yiwu, China., Song Y; Department of Ultrasound Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China., Wang Y; Center for Metabolism Research, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University , Yiwu, China., Zhang H; Center for Metabolism Research, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University , Yiwu, China., Li J; Center for Metabolism Research, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University , Yiwu, China., Qiu X; Center for Metabolism Research, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University , Yiwu, China., Pu M; Center for Metabolism Research, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University , Yiwu, China., Liu X; Center for Metabolism Research, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University , Yiwu, China., Peng C; National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences , Shanghai, China., Neculai D; Center for Metabolism Research, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University , Yiwu, China., Sun Q; Center for Metabolism Research, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University , Yiwu, China., Zhou T; Center for Metabolism Research, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University , Yiwu, China., Huang P; Department of Ultrasound Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China., Liu W; Center for Metabolism Research, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University , Yiwu, China.; Department of Ultrasound Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Jazyk:	angličtina
Zdroj:	The Journal of cell biology [J Cell Biol] 2024 Nov 04; Vol. 223 (11). Date of Electronic Publication: 2024 Aug 28.
DOI:	10.1083/jcb.202308099
Abstrakt:	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. (© 2024 Huang et al.)
Databáze:	MEDLINE
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