Cited by 93Autophagy in Disease and TherapyCellular transport and secretionCell death mechanisms and regulation

ATG9A protects the plasma membrane from programmed and incidental permeabilization

Open access
Claude-Taupin, Aurore, Jia, Jingyue, Bhujabal, Zambarlal, Garfa-Traoré, Meriem, Kumar, Suresh, da Silva, Gustavo Peixoto Duarte, Javed, Ruheena, Gu, Yuexi +16 more·2021·Nature Cell Biology

Abstract

The integral membrane protein ATG9A plays a key role in autophagy. It displays a broad intracellular distribution and is present in numerous compartments, including the plasma membrane (PM). The reasons for the distribution of ATG9A to the PM and its role at the PM are not understood. Here, we show that ATG9A organizes, in concert with IQGAP1, components of the ESCRT system and uncover cooperation between ATG9A, IQGAP1 and ESCRTs in protection from PM damage. ESCRTs and ATG9A phenocopied each other in protection against PM injury. ATG9A knockouts sensitized the PM to permeabilization by a broad spectrum of microbial and endogenous agents, including gasdermin, MLKL and the MLKL-like action of coronavirus ORF3a. Thus, ATG9A engages IQGAP1 and the ESCRT system to maintain PM integrity. Claude-Taupin et al. show that ATG9A mediates protection against plasma membrane damage in diverse biological contexts through a mechanism involving IQGAP1 and ESCRTs.

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  • ATG9A, together with IQGAP1 and ESCRT proteins, protects against plasma membrane damage.

    “Together with IQGAP1 and ESCRT proteins, ATG9A has further been shown to protect against plasma membrane damage [52].”

    From miRNA family miR-29 inhibits PINK1-PRKN signaling via ATG9A (2026) · cites this paper as [52]

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Authors
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., Wang, F., da Costa, L. J., Pallikkuth, S., Lidke, K. A., Mauthe, M., Verlhac, P., Uchiyama, Y., Salemi, M., Phinney, B., Tooze, S. A., Mari, M. C., Johansen, T., Reggiori, F., & Deretic, V.
Affiliations
  • University of New Mexico (US)
  • UiT The Arctic University of Norway (NO)
  • University Medical Center Groningen (NL)
  • Juntendo University (JP)
  • University of California, Davis (US)
  • The Francis Crick Institute (GB)
Corresponding author
Deretic, Vojo
Venue
Nature Cell Biology
Published
2021-07-12
Volume
23
Issue
8
Pages
846-858
ISSN
  • 1465-7392 (ISSN-L)
  • 1476-4679
OpenAlex
W3177552861
Cited by
92
References
76
Citations by year
2026: 15 · 2025: 23 · 2024: 16 · 2023: 16 · 2022: 15 · 2021: 7
FWCI
9.91
Type
journal article
Language
en
Open access
Locations
  • Nature Cell Biology (publishedVersion, other-oa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • NORA - Norwegian Open Research Archives (submittedVersion, other-oa)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
Funders
  • U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (R37AI042999, R01AI042999)
  • U.S. Department of Health & Human Services | NIH | 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 › Molecular Biology › Cell death mechanisms and regulation
Keywords
ATG9A, plasma membrane integrity, membrane permeabilization, IQGAP1, autophagy, gasdermin, MLKL, membrane repair, programmed cell death
MeSH terms
Autophagosomes, Autophagy-Related Proteins, Cell Membrane, HeLa Cells, Humans, Membrane Proteins, Immunoblotting, Microscopy, Confocal, Protein Transport, Vesicular Transport Proteins, Immunoprecipitation, HEK293 Cells

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