Atg9 is a lipid scramblase that mediates autophagosomal membrane expansion
Abstract
The molecular function of Atg9, the sole transmembrane protein in the autophagosome-forming machinery, remains unknown. Atg9 colocalizes with Atg2 at the expanding edge of the isolation membrane (IM), where Atg2 receives phospholipids from the endoplasmic reticulum (ER). Here we report that yeast and human Atg9 are lipid scramblases that translocate phospholipids between outer and inner leaflets of liposomes in vitro. Cryo-EM of fission yeast Atg9 reveals a homotrimer, with two connected pores forming a path between the two membrane leaflets: one pore, located at a protomer, opens laterally to the cytoplasmic leaflet; the other, at the trimer center, traverses the membrane vertically. Mutation of residues lining the pores impaired IM expansion and autophagy activity in yeast and abolished Atg9's ability to transport phospholipids between liposome leaflets. These results suggest that phospholipids delivered by Atg2 are translocated from the cytoplasmic to the luminal leaflet by Atg9, thereby driving autophagosomal membrane expansion.
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ATG9A acts as a lipid scramblase facilitating membrane expansion.
“ATG9A was more recently shown to act as a lipid scramblase facilitating membrane expansion [50, 51].”
From miRNA family miR-29 inhibits PINK1-PRKN signaling via ATG9A (2026) · cites this paper as [51]
Cites
Fiji: an open-source platform for biological-image analysis
Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., et al. (2012) · Nature Methods · doi:10.1038/nmeth.2019 · Cited by 66,890 · see citing works
Kihara, A., Noda, T., Ishihara, N., & Ohsumi, Y. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.152.3.519 · Cited by 1,004 · see citing works
Self-citationAn Atg9-containing compartment that functions in the early steps of autophagosome biogenesis
Mari, M., Griffith, J., Rieter, E., Krishnappa, L., Klionsky, D. J., & Reggiori, F. (2010) · Journal of Cell Biology · doi:10.1083/jcb.200912089 · Cited by 491 · see citing works
Diverse Cellular Roles of Autophagy
Morishita, H., & Mizushima, N. (2019) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100818-125300 · Cited by 376 · see citing works
Structure of Human ATG9A, the Only Transmembrane Protein of the Core Autophagy Machinery
Guardia, C. M., Tan, X.-F., Lian, T., Rana, M. S., Zhou, W., Christenson, E. T., Lowry, A. J., Faraldo-Gómez, J. D., Bonifacino, J. S., Jiang, J., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107837 · Cited by 163 · see citing works
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Mechanisms of Selective Autophagy
Lamark, T., & Johansen, T. (2021) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-120219-035530 · Cited by 429 · see citing works
Gómez-Virgilio, L., Silva-Lucero, M.-D.-C., Flores-Morelos, D.-S., Gallardo-Nieto, J., Lopez-Toledo, G., Abarca-Fernandez, A.-M., Zacapala-Gómez, A.-E., Luna-Muñoz, J., Montiel-Sosa, F., Soto-Rojas, L. O., et al. (2022) · Cells · doi:10.3390/cells11152262 · Cited by 431 · see citing works
ATG9A protects the plasma membrane from programmed and incidental permeabilization
Claude-Taupin, A., Jia, J., Bhujabal, Z., Garfa-Traoré, M., Kumar, S., da Silva, G. P. D., Javed, R., Gu, Y., Allers, L., Peters, R., et al. (2021) · Nature Cell Biology · doi:10.1038/s41556-021-00706-w · Cited by 92 · see citing works
miRNA family miR-29 inhibits PINK1-PRKN signaling via ATG9A
Markham, B. N., Ramnarine, C., Kim, S., Grever, W. E., Soto-Beasley, A. I., Heckman, M. G., Ren, Y., Osborne, A. C., Kehili, M., Bhagwate, A. V., et al. (2026) · Molecular Neurodegeneration Advances · doi:10.1186/s44477-026-00029-w
- Authors
- Matoba, K., Kotani, T., Tsutsumi, A., Tsuji, T., Mori, T., Noshiro, D., Sugita, Y., Nomura, N., Iwata, S., Ohsumi, Y., Fujimoto, T., Nakatogawa, H., Kikkawa, M., & Noda, N. N.
- Affiliations
- Tokyo Institute of Technology (JP)
- The University of Tokyo (JP)
- Juntendo University (JP)
- RIKEN (JP)
- Kyoto University (JP)
- ORCID
- Venue
- Nature Structural & Molecular Biology
- Published
- 2020-10-26
- Volume
- 27
- Issue
- 12
- Pages
- 1185-1193
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- OpenAlex
- W3093716916
- Cited by
- 430
- References
- 5
- Citations by year
- 2026: 48 · 2025: 72 · 2024: 79 · 2023: 79 · 2022: 77 · 2021: 73 · 2020: 2
- FWCI
- 41.70
- Type
- journal article
- Language
- en
- Update notices
- correction (2020-11-12)
- Open access
- closed
- Locations
- Nature Structural & Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- MEXT | JST | Core Research for Evolutional Science and Technology (JPMJCR13M7, JPMJCR14M1)
- MEXT | Japan Society for the Promotion of Science (18H03989, 19H05707, 15K21608, 18K06097, 19K16071, 19K07265, 19K06532, 19K16344, 26119006, 19H05645, 19H05708, 15H05902, 18H04023, 17H01430)
- Takeda Science Foundation
- Naito Foundation
- Japan Agency for Medical Research and Development (JP19am0101001, JP19am0101079, 19am0101079)
- 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 › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- Atg9, lipid scramblase, isolation membrane, ATG2, phospholipid translocation, autophagy, Schizosaccharomyces pombe
- MeSH terms
- Autophagosomes, Autophagy-Related Proteins, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Red Fluorescent Protein, Binding Sites, Biological Transport, Humans, Lipid Bilayers, Luminescent Proteins, Membrane Proteins, Models, Molecular, Phospholipids, Protein Binding, Proteolipids, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Gene Expression, Cryoelectron Microscopy, Saccharomyces cerevisiae Proteins, Vesicular Transport Proteins, Green Fluorescent Proteins, Protein Interaction Domains and Motifs, Protein Multimerization
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