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Autophagy
Article . 2025 . Peer-reviewed
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ATG9A controls all stages of autophagosome biogenesis

Authors: Ruheena Javed; Muriel Mari; Einar Trosdal; Thabata Lopes Alberto Duque; Masroor Paddar; Lee Allers; Prithvi Akepati; +3 Authors

ATG9A controls all stages of autophagosome biogenesis

Abstract

Canonical autophagy is an intracellular pathway that degrades and recycles cellular components. A key step of this pathway is the formation of double-membraned organelles, known as autophagosomes, an emblematic feature of macroautophagy. For convenience, the formation of autophagosomes can be categorized into sequential steps, initiation (X), expansion (Y) and closure (Z). ATG9A is an integral membrane protein known for its role in the X and Y steps. whereby it organizes phagophore membrane assembly and its growth. Here, we report a previously unappreciated function of mammalian ATG9A in directing the last step Z. In particular, ATG9A partners with the key ESCRT-III component CHMP2A through IQGAP1 to facilitate autophagosome closure. Thus, ATG9A orchestrates all stages of autophagosome membrane biogenesis, from phagophore initiation to its closure. This makes ATG9A a unique ATG factor that works as a central hub in autophagosome biogenesis.Abbreviation: ATG9A autophagy related 9A; CCCP carbonyl cyanide m-chlorophenylhydrazone; Co-IP co-immunoprecipitation; ESCRT endosomal sorting complexes required for transport; EBSS Earle's balanced salt solution; ER endoplasmic reticulum; HCM high-content microscopy; HT HaloTag; LC-MS/MS liquid chromatography-tandem mass spectrometry; KO knockout; MPL membrane permeant ligand; MIL membrane impermeant ligand; Mtb Mycobacterium tuberculosis; SolVit sealing of organellar limiting membranes in vitro; TMR tetramethylrhodamine; WT wild type.

Keywords

Mice, Endosomal Sorting Complexes Required for Transport/metabolism, Autophagy-Related Proteins/metabolism, Vesicular Transport Proteins/metabolism, Humans, Animals, Autophagosomes/metabolism, Membrane Proteins/metabolism, Autophagy/physiology, HeLa Cells

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
1
Average
Average
Average
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