Lactate is a bridge linking glycolysis and autophagy through lactylation.

IF 14.6 1区生物学 Q1 CELL BIOLOGY Autophagy Pub Date : 2023-12-01 Epub Date: 2023-08-18 DOI:10.1080/15548627.2023.2246356

Weixia Sun, Mengshu Jia, Yingyan Feng, Xiawei Cheng

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引用次数: 2

Abstract

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.

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乳酸是连接糖酵解和自噬的桥梁。

乳酸是由丙酮酸通过乳酸脱氢酶（LDH）产生的糖酵解产物，在生理和病理过程中起着重要作用。然而，乳酸是否调节自噬仍然未知。我们最近报道，在营养缺乏条件下，LDHA在丝氨酸196被ULK1（unc-51样激酶1）磷酸化，促进乳酸的产生。然后，乳酸盐通过酰基转移酶KAT5/TIP60介导PIK3C3/VPS34在赖氨酸356和赖氨酸781处的乳酰化。PIK3C3/VPS34乳酸化增强了PIK3C3/VPS34与BECN1（beclin 1，自噬相关）、ATG14和UVRAG的结合，增加了PIK3C3/VPS34脂质激酶活性，促进了大自噬/自噬，并促进了内溶酶体降解途径。PIK3C3/VPS34高乳酸化诱导自噬，并在骨骼肌稳态和癌症进展中发挥重要作用。总的来说，这项研究描述了自噬调节机制和两个高度保守的生命过程的整合：糖酵解和自噬。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Autophagy 生物-细胞生物学

CiteScore

21.30

自引率

2.30%

发文量

277

审稿时长

1 months

期刊介绍： Autophagy is a peer-reviewed journal that publishes research on autophagic processes, including the lysosome/vacuole dependent degradation of intracellular material. It aims to be the premier journal in the field and covers various connections between autophagy and human health and disease, such as cancer, neurodegeneration, aging, diabetes, myopathies, and heart disease. Autophagy is interested in all experimental systems, from yeast to human. Suggestions for specialized topics are welcome. The journal accepts the following types of articles: Original research, Reviews, Technical papers, Brief Reports, Addenda, Letters to the Editor, Commentaries and Views, and Articles on science and art. Autophagy is abstracted/indexed in Adis International Ltd (Reactions Weekly), EBSCOhost (Biological Abstracts), Elsevier BV (EMBASE and Scopus), PubMed, Biological Abstracts, Science Citation Index Expanded, Web of Science, and MEDLINE.