《生命科学》 2026, 38(5): 859-860

蛋白质乳酸化在线粒体质量控制中的作用研究进展

王 祯^1,2 , 朱 琳^1,3,*

¹广州体育学院运动与健康学院，广州 510500 ²广州体育学院体卫融合创新发展研究中心，广州 510500 ³广州体育学院粤港澳大湾区体育科学创新研究中心，广州 510500

摘　要：

线粒体是细胞能量供应与代谢调控的中心，依赖质量控制系统进行自身结构、功能和数量调整。乳酸化修
饰（lactylation）是一种由乳酸驱动、可作用于组蛋白与非组蛋白上的新型翻译后修饰形式，既通过上调动力蛋白相关蛋白1（Drp1）表达或改变线粒体分裂蛋白1（Fis1）功能，诱导线粒体分裂；又可影响RBR结构域E3泛素连接酶（Parkin）、BCL2相互作用蛋白3（BNIP3）、线粒体翻译延伸因子Tu（Tufm）的表达与功能，参与线粒体自噬调控，但内在机制尚未完全阐明。本文就乳酸化修饰在调控线粒体质量控制中的作用及机制作一综述，以期为后续相关研究提供参考。

通讯作者：朱 琳 , Email:11251@gzsport.edu.cn

Research progress on the role of protein lactylation in mitochondrial quality control

WANG Zhen^1,2 , ZHU Lin^1,3,*

¹School of Sport and Health, Guangzhou Sport University, Guangzhou 510500, China ²Research Center for Innovative Development of Sports and Healthcare Integration, Guangzhou Sport University, Guangzhou 510500, China ³Innovative Research Center for Sports Science in the Guangdong-Hong Kong-Macao Greater Bay Area, Guangzhou Sport University, Guangzhou 510500, China

Abstract:

Mitochondria are central organelles responsible for cellular energy production and metabolic regulation, relying on a quality control system to dynamically adjust their function, structure, and quantity. Mitochondrial quality control (MQC)  disruption is closely associated with the development of multiple diseases. Lactylation, a lactate-derived post-translational  modification, has emerged as a key regulator of mitochondrial structure, dynamics, and mitophagy by modulating the expression and function of MQC-related proteins, although its mechanisms remain incompletely defined. This review summarizes current advances on the roles and molecular mechanisms of lactylation in MQC, with the aim of providing  insights into future research in this field. The main conclusions are as follows: (a) Lactylation regulates mitochondrial structure by modifying outer membrane protein VDAC1 and inner membrane protein Mic10, thereby altering mitochondrial metabolic function. It also directly modulates mitochondrial metabolism by enhancing MDH2 activity and  ACAA2 expression, or inhibiting enzymes such as ATP5F1, CS, HADHA, PDHA1, and CPT2. (b) Lactylation promotes Drp1-dependent mitochondrial fission (e.g., Fis1 K20la facilitates Drp1 binding, and Hsp60 K469/K473la induces Drp1 Ser616 phosphorylation), whereas its impact on mitochondrial fusion remains unclear. (c) Lactylation exerts bidirectional regulation on mitophagy. For instance, H3K18la activates mitophagy by upregulating PSMD14, MICU3,  YTHDF2, Parkin, and BNIP3, and P4HB K311la indirectly promotes PINK1/Parkin-dependent mitophagy. In contrast,  ALDH2 K52la and Tufm K286la exert inhibitory effects on mitophagy. Under pathological conditions, lactylation and MQC can form a vicious cycle of “lactate accumulation–MQC dysfunction”, indicating that targeting lactylation may represent a  promising therapeutic strategy. However, research in this area is still at an early stage. Future   studies should: (1) clarify the causal relationship and reciprocal regulation between lactylation and mitochondrial function; (2) define the role of lactylation in mitochondrial biogenesis and proteostasis; and (3) determine whether exercise-induced lactate elevation improves  mitochondrial quality via lactylation. Addressing these questions will deepen our understanding of lactylation in physiology  and pathology and may reveal novel targets and strategies for disease prevention and treatment.

Communication Author：ZHU Lin , Email:11251@gzsport.edu.cn