文献类型：期刊文献

英文题名：Lactate is a bridge linking glycolysis and autophagy through lactylation

作者：Sun, Weixia[1];Jia, Mengshu[1];Feng, Yingyan[1];Cheng, Xiawei[1,2]

机构：[1]East China Univ Sci & Technol, Optogenet & Synthet Biol Interdisciplinary Res Ctr, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, Sch Pharm,State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[2]East China Univ Sci & Technol, Optogenet & Synthet Biol Interdisciplinary Res Ctr, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, Sch Pharm,State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2023

卷号：19

期号：12

起止页码：3240

外文期刊名：AUTOPHAGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001050449700001)】；

基金：This study was supported by the National Key Research and Development Program of China (2021YFC2101100 to X.C.) and the National Nature Science Foundation of China (32170764 to X.C.).

语种：英文

摘要：Lactate is a glycolysis product that is produced from pyruvate by LDH (lactate dehydrogenase) and plays an important role in physiological and pathological processes. However, whether lactate regulates autophagy is still unknown. We recently reported that LDHA is phosphorylated at serine 196 by ULK1 (unc-51 like kinase 1) under nutrient-deprivation conditions, promoting lactate production. Then, lactate mediates PIK3C3/VPS34 lactylation at lysine 356 and lysine 781 via acyltransferase KAT5/TIP60. PIK3C3/VPS34 lactylation enhances the association of PIK3C3/VPS34 with BECN1 (beclin 1, autophagy related), ATG14 and UVRAG, increases PIK3C3/VPS34 lipid kinase activity, promotes macroautophagy/autophagy and facilitates the endolysosomal degradation pathway. PIK3C3/VPS34 hyperlactylation induces autophagy and plays an essential role in skeletal muscle homeostasis and cancer progression. Overall, this study describes an autophagy regulation mechanism and the integration of two highly conserved life processes: glycolysis and autophagy.