ATG9 is often described as the sole transmembrane protein among the core
autophagy factors. The mammalian ATG9A is notorious for trafficking through
numerous cellular compartments including the plasma membrane. The
reasons for ATG9As wide intracellular distribution and its role at the PM are not
fully understood. Here we show that ATG9A intimately interacts with components
of the ESCRT system. Employing proteomic analyses with APEX2-ATG9A we
identified a number of ESCRTs as ATG9A interactors, including TSG101 and
ALIX, and uncovered cooperation between ATG9A and ESCRTs in protection
against PM damage. ATG9A knockouts sensitized PM to permeabilization by a
broad spectrum of agents including gasdermin and Mycobacterium tuberculosis.
ESCRTs phenocopied ATG9A in protection against PM injury. Thus, in addition
to its function in autophagy, ATG9A is a component of the ESCRT system
engaged in the repair of PM
[doi:10.25345/C5WH48]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: ATG9 ; ATG9A ; APEX2-ATG9A ; ESCRT system ; Plasma membrane
Principal Investigators: (in alphabetical order) |
Vojo Deretic, University of New Mexico Health Sciences Center, USA |
Submitting User: | brettsp1 |
Claude-Taupin A, Jia J, Bhujabal Z, Garfa-Traoré M, Kumar S, da Silva GPD, Javed R, Gu Y, Allers L, Peters R, Wang F, da Costa LJ, Pallikkuth S, Lidke KA, Mauthe M, Verlhac P, Uchiyama Y, Salemi M, Phinney B, Tooze SA, Mari MC, Johansen T, Reggiori F, Deretic V.
ATG9A protects the plasma membrane from programmed and incidental permeabilization.
Nat Cell Biol. Epub 2021 Jul 12.
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