细胞生物学
自噬
小泡
转运蛋白
化学
生物
线粒体
膜
生物化学
细胞凋亡
作者
Zifan Tang,Yoshinori Takahashi,Haiyan He,Tatsuya Hattori,Chong Chen,Xinwen Liang,Han Chen,Michelle Young,Honggang Wang
出处
期刊:Cell Reports
[Elsevier]
日期:2019-08-01
卷期号:28 (7): 1744-1757.e5
被引量:85
标识
DOI:10.1016/j.celrep.2019.07.036
摘要
Summary
During autophagy, phagophores grow into double-membrane vesicles called autophagosomes, but the underlying mechanism remains unclear. Here, we show a critical role of Atg2A in phagophore expansion. Atg2A translocates to the phagophore at the mitochondria-associated ER membrane (MAM) through a C-terminal 45-amino acid domain that we have termed the MAM localization domain (MLD). Proteomic analysis identifies the outer mitochondrial membrane protein TOM40 as a MLD-interacting partner. The Atg2A-TOM40 interaction is responsible for MAM localization of Atg2A and requires the TOM receptor protein TOM70. In addition, Atg2A interacts with Atg9A by a region within its N terminus. Inhibition of either Atg2A-TOM40 or Atg2A-Atg9A interactions impairs phagophore expansion and accumulates Atg9A-vesicles in the vicinity of autophagic structures. Collectively, we propose a model that the TOM70-TOM40 complex recruits Atg2A to the MAM for vesicular and/or non-vesicular lipid transport into the expanding phagophore to grow the size of autophagosomes for efficient autophagic flux.
科研通智能强力驱动
Strongly Powered by AbleSci AI