ATG9A controls all stages of autophagosome biogenesis
Open accessAbstract
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.
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ATG9A is not incorporated into autophagosomes and plays an essential role in their formation, expansion and closure.
“ATG9A, which itself is not incorporated into autophagosomes, is known to play an essential role for their formation, expansion and closure [47, 48].”
From miRNA family miR-29 inhibits PINK1-PRKN signaling via ATG9A (2026) · cites this paper as [48]
The Abstract and Figure 1 description say ATG9A contributes to phagophore initiation, expansion, and closure. They do not say that ATG9A is absent from completed autophagosomes, so the non-incorporation part is unsupported by our copy. (LLM, conf=0.87)
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References 1 · Cited by 4
Research works printed but not linked: 1
- Javed R, Mari M, Trosdal E, et al. ATG9A facilitates the closure of mammalian autophagosomes. J Cell Biol. 2025;224(2):e202404047. doi: 10.1083/jcb.202404047 · DOI
- Authors
- Javed, R., Mari, M., Trosdal, E., Lopes Alberto Duque, T., Paddar, M., Allers, L., Akepati, P., Mudd, M. H., Reggiori, F., & Deretic, V.
- Affiliations
- University of New Mexico (US)
- Aarhus University (DK)
- University of New Mexico Health Sciences Center
- University of New Mexico Health Sciences Center (US)
- Corresponding author
- Deretic, Vojo
- ORCID
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2025-04-27
- Volume
- 21
- Issue
- 8
- Pages
- 1859-1861
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC12282988
- OpenAlex
- W4409519179
- Cited by
- 4
- References
- 1
- Citations by year
- 2026: 3 · 2025: 1
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- green
- pmc.ncbi.nlm.nih.gov
- Locations
- Autophagy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R37AI042999)
- National Institute of General Medical Sciences (P20GM121176)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- ATG9A, autophagosome formation, CHMP2A, IQGAP1, ESCRT-III, membrane biogenesis
- MeSH terms
- Autophagosomes, Autophagy-Related Proteins, Animals, Autophagy, HeLa Cells, Humans, Membrane Proteins, Vesicular Transport Proteins, Mice, Endosomal Sorting Complexes Required for Transport
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