LC3脂质化修饰的机制和功能研究进展

Molecular mechanisms and functions of LC3 lipidation

LC3(包括LC3/GABARAP蛋白家族所有成员)的脂质化修饰是细胞自噬过程中的关键事件.LC3完成脂质化修饰后,由水溶性形式转化为膜结合形式,在自噬小体的形成、自噬底物的招募和自噬小体-溶酶体融合等阶段均发挥重要作用.包括营养状态和病原菌入侵在内的多种细胞内外刺激信号均可参与调控LC3的脂质化修饰过程.近年来的研究发现,脂质化的LC3不仅可以靶向细胞内双层膜的自噬小体,也可以靶向细胞内多种单层膜结构,如吞噬体和溶酶体等,参与调控细胞的内吞和微自噬等生物学过程.本文将围绕LC3脂质化修饰的机制和功能综述近年来的相关研究进展.

Lipidation of LC3(including all LC3/GABARAP family proteins)is a key event of autophagy process.LC3 obtains membranebound capacity via conjugation with phosphatidyl ethanolamine under the assistance of two ubiquitination-like systems.Membranebound LC3 controls several pivotal steps of autophagy,including autophagosome formation,cargo recruitment and autophagosomelysosome fusion.Intriguingly,lipidated LC3 can also target to some intracellular single membrane vesicles,including phagosome and lysosome,and participates in several autophagy-independent processes,such as phagocytosis and microautophagy.Various intracellular and extracellular stimuli,such as nutrient deprivation and pathogen invasion,have been demonstrated to target LC3 lipidation to control autophagy,phagocytosis and other related processes.In this paper,we review the recent studies on the molecular mechanisms and physiological functions of LC3 lipidation in mammalian cells.