Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1-9 |
| Number of pages | 9 |
| Journal | Journal of cell science |
| Volume | 137 |
| Issue number | 4 |
| DOIs | |
| State | Published - 2024 |
Funding
A.R.v.V. was supported by a European Molecular Biology Organization (EMBO) long-term fellowship (EMBO ALTF 325-2017). H.B.J.J., F.I., P.A.F., J.M.S., S.A.T., were supported by The Francis Crick Institute which receives its core funding from Cancer Research UK (CC2134, CC2058), the Medical Research Council (CC2134, CC2058). This research was funded in whole, or in part, by the Wellcome Trust (CC2134, CC2058). A.R.v.V. and S.A.T. received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 788708. Open Access funding provided by The Francis Crick Institute. Deposited in PMC for immediate release.
Keywords
- ATG9A interactome
- Autophagy
- Lipid trafficking
- Mass spectrometry
- VPS13
ASJC Scopus subject areas
- Cell Biology