Nature Communications· 2026Q1
A lipid transfer-dependent feedback loop activates ATG9A compartments in autophagy initiation
- 3citations
- Q1SCImago
- 2026year
Short summary
Autophagy initiation relies on ATG9A compartments, which are activated by a lipid transfer-driven feedback loop involving ATG2A and ATG8 proteins, enabling PI3P production and phagophore expansion.
AI-generated from the title and abstract; the full text is not read.
Key points
- ATG9A compartments are essential for phagophore assembly in autophagy.
- ATG2A mediates lipid transfer, including PI, into ATG9A compartments.
- ATG8 proteins enhance ATG2A-mediated lipid transfer.
- ATG2A is required for PI3P appearance on ATG9A compartments.
- A lipid transfer-driven feedback loop activates ATG9A compartments for phagophore expansion.
AI-generated from the title and abstract; the full text is not read.
Abstract
Abstract Autophagy degrades cellular material by sequestering it within autophagosomes, which form de novo from precursors called phagophores. Phagophore assembly and expansion require ATG9A-positive seed compartments, the lipid transfer protein ATG2A, and the class III phosphatidylinositol 3-phosphate kinase complex I (PI3KC3-C1). PI3KC3-C1 synthesizes phosphatidylinositol 3-phosphate (PI3P), a key lipid that drives downstream processes for phagophore expansion, including ATG8 lipidation. We find that ATG9A compartments contain only traces of phosphatidylinositol (PI), likely insufficient for efficient PI3P production or recruitment of PI3P-binding effectors. Nevertheless, ATG2A is recruited to these compartments and mediates lipid transfer, including PI, into them. Remarkably, even without detectable PI3P, ATG9A compartments are direct substrates for ATG8 lipidation, and ATG8 proteins themselves enhance ATG2A-mediated lipid transfer. In cells, ATG2A is essential for the appearance of PI3P on ATG9A compartments. Our findings support a model in which a lipid transfer-driven feedback loop activates ATG9A compartments for phagophore expansion.
The authors' abstract, as published at the source. Nature Communications, 2026 · DOI ↗
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Field: Epidemiology
EpidemiologyMedicine