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Exploring the ATG9A interactome uncovers interaction with VPS13A.

Alexander R van VlietHarold B J JefferiesPeter A FaullJessica ChadwickFairouz IbrahimMark J SkehelSharon A Tooze
Published in: Journal of cell science (2024)
ATG9A, a transmembrane protein of the core autophagy pathway, cycles between the Golgi, endosomes and a vesicular compartment. ATG9A was recently shown to act as a lipid scramblase, and this function is thought to require its interaction with another core autophagy protein, ATG2A, which acts as a lipid transfer protein. Together, ATG9A and ATG2A are proposed to function to expand the growing autophagosome. However, ATG9A is implicated in other pathways including membrane repair and lipid droplet homeostasis. To elucidate other ATG9A interactors within the autophagy pathway, or interactors beyond autophagy, we performed an interactome analysis through mass spectrometry. This analysis revealed a host of proteins involved in lipid synthesis and trafficking, including ACSL3, VPS13A and VPS13C. Furthermore, we show that ATG9A directly interacts with VPS13A and forms a complex that is distinct from the ATG9A-ATG2A complex.
Keyphrases
  • cell death
  • mass spectrometry
  • signaling pathway
  • endoplasmic reticulum stress
  • oxidative stress
  • fatty acid
  • single cell
  • high throughput
  • liquid chromatography