Actions for TOM40 Targets Atg2 to Mitochondria-Associated ER Membranes for Phagophore Expansion

Email RIS file
Bookmark
Report an Issue

TOM40 Targets Atg2 to Mitochondria-Associated ER Membranes for Phagophore Expansion

Published
2019.
Physical Description
1 online resource
Additional Creators
Chen, C., Chen, Han, Hattori, Tatsuya, He, Haiyan, Liang, Xinwen, Takahashi, Yoshinori, Tang, Zhenyuan, Wang, Hong-Gang, and Young, Megan M.
Access Online

Availability

I Want It
I Want It

Finding items...

Restrictions on Access
Open Access Unrestricted online access
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. Tang et al. show that human Atg2 is a key regulator for phagophore expansion. TOM40/70 directs Atg2A to MAM to mediate phagophore expansion. On the MAM, Atg2A facilitates Atg9-vesicle delivery and retrograde trafficking to promote phagophore expansion and efficient autophagic flux."
Collection
Penn State Faculty and Staff Researcher Metadata Database Collection.
Note
Academic Journal Article
Part Of
Cell Reports
28:7, pp. 1744-1757.e5
2211-1247
View MARC record | catkey: 31201290