ArticleNature structural & molecular biology2020
Structure, lipid scrambling activity and role in autophagosome formation of ATG9A.
Article in Nature structural & molecular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 184 papers.
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Who cites it
184 citing papers in PubMed, 306 citations in OpenAlex.
- Emerging mechanisms of ATG8-independent non-canonical autophagy.Journal of physiology and biochemistry · 2026Review
- Atg23 prevents aberrant fusion of Atg9 vesicles during delivery to autophagosome formation sites.The EMBO journal · 2026Article
- A lipid transfer-dependent feedback loop activates ATG9A compartments in autophagy initiation.Nature communications · 2026Article
- Regulation and roles of mammalian mitophagy.Nature reviews. Molecular cell biology · 2026Review
- Article
- Allele frequency trajectories across age groups reveal ongoing natural selection shaping disease susceptibility.American journal of human genetics · 2026Article
- Diverse applications of volume CLEM analysis in cell biology: brief overview, unique techniques and recent notable works.Microscopy (Oxford, England) · 2026Review
- Review
- ATG9A is an essential host factor for parechovirus RNA replication.Journal of virology · 2026Article
- TRIM21 induces selective autophagy of viruses and bacteria.Molecular cell · 2026Article
- The Human Autophagy Core Complexes.Annual review of biochemistry · 2026Review
- Review
- ATG9B regulates mitochondrial integrity and apoptotic tumor cell death.Molecular biology of the cell · 2026Article
- Review
- Core principles of autophagy initiation mechanisms.Nature structural & molecular biology · 2026Review
- ER membrane receptors engage core autophagy machinery to initiate ER-phagy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- Vacuolar Membrane Protein 1 and Transmembrane Protein 41B in Action: At the Right Place, With the Right Strength.Cellular and molecular gastroenterology and hepatology · 2026Article
- miRNA family miR-29 inhibits PINK1-PRKN signaling via ATG9A.Molecular neurodegeneration advances · 2026Article
- The AP-4 accessory protein tepsin exhibits multivalent binding to LC3B.Advances in biological regulation · 2026Article
124 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
De novo formation of the double-membrane compartment autophagosome is seeded by small vesicles carrying membrane protein autophagy-related 9 (ATG9), the function of which remains unknown. Here we find that ATG9A scrambles phospholipids of membranes in vitro. Cryo-EM structures of human ATG9A reveal a trimer with a solvated central pore, which is connected laterally to the cytosol through the cavity within each protomer. Similarities to ABC exporters suggest that ATG9A could be a transporter that uses the central pore to function. Moreover, molecular dynamics simulation suggests that the central pore opens laterally to accommodate lipid headgroups, thereby enabling lipids to flip. Mutations in the pore reduce scrambling activity and yield markedly smaller autophagosomes, indicating that lipid scrambling by ATG9A is essential for membrane expansion. We propose ATG9A acts as a membrane-embedded funnel to facilitate lipid flipping and to redistribute lipids added to the outer leaflet of ATG9 vesicles, thereby enabling growth into autophagosomes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.