Function and molecular mechanism of N-terminal acetylation in autophagy
Tianyun Shen,
Lan Jiang,
Xinyuan Wang,
Qingjia Xu,
Lu Han,
Shiyan Liu,
Ting Huang,
Hongyan Li,
Lunzhi Dai,
Huihui Li,
Kefeng Lu
Affiliations
Tianyun Shen
Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and The Research Units of West China, Chinese Academy of Medical Sciences, Chengdu 610041, China
Lan Jiang
Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and The Research Units of West China, Chinese Academy of Medical Sciences, Chengdu 610041, China
Xinyuan Wang
National Clinical Research Center for Geriatrics and Department of General Practice, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China
Qingjia Xu
Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and The Research Units of West China, Chinese Academy of Medical Sciences, Chengdu 610041, China
Lu Han
Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and The Research Units of West China, Chinese Academy of Medical Sciences, Chengdu 610041, China
Shiyan Liu
Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and The Research Units of West China, Chinese Academy of Medical Sciences, Chengdu 610041, China
Ting Huang
Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and The Research Units of West China, Chinese Academy of Medical Sciences, Chengdu 610041, China
Hongyan Li
Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
Lunzhi Dai
National Clinical Research Center for Geriatrics and Department of General Practice, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China; Corresponding author
Huihui Li
Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and The Research Units of West China, Chinese Academy of Medical Sciences, Chengdu 610041, China; West China Second University Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China; Corresponding author
Kefeng Lu
Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and The Research Units of West China, Chinese Academy of Medical Sciences, Chengdu 610041, China; Corresponding author
Summary: Acetyl ligation to the amino acids in a protein is an important posttranslational modification. However, in contrast to lysine acetylation, N-terminal acetylation is elusive in terms of its cellular functions. Here, we identify Nat3 as an N-terminal acetyltransferase essential for autophagy, a catabolic pathway for bulk transport and degradation of cytoplasmic components. We identify the actin cytoskeleton constituent Act1 and dynamin-like GTPase Vps1 (vacuolar protein sorting 1) as substrates for Nat3-mediated N-terminal acetylation of the first methionine. Acetylated Act1 forms actin filaments and therefore promotes the transport of Atg9 vesicles for autophagosome formation; acetylated Vps1 recruits and facilitates bundling of the SNARE (soluble N-ethylmaleimide-sensitive factor activating protein receptor) complex for autophagosome fusion with vacuoles. Abolishment of the N-terminal acetylation of Act1 and Vps1 is associated with blockage of upstream and downstream steps of the autophagy process. Therefore, our work shows that protein N-terminal acetylation plays a critical role in controlling autophagy by fine-tuning multiple steps in the process.
