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Mammalian ATG8 proteins maintain autophagosomal membrane integrity through ESCRTs.
Javed, Ruheena; Jain, Ashish; Duque, Thabata; Hendrix, Emily; Paddar, Masroor Ahmad; Khan, Sajjad; Claude-Taupin, Aurore; Jia, Jingyue; Allers, Lee; Wang, Fulong; Mudd, Michal; Timmins, Graham; Lidke, Keith; Rusten, Tor Erik; Akepati, Prithvi Reddy; He, Yi; Reggiori, Fulvio; Eskelinen, Eeva-Liisa; Deretic, Vojo.
Afiliación
  • Javed R; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • Jain A; Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • Duque T; Faculty of Medicine, University of Oslo, Oslo, Norway.
  • Hendrix E; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • Paddar MA; Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • Khan S; Department of Chemistry & Chemical Biology, The University of New Mexico, Albuquerque, NM, USA.
  • Claude-Taupin A; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • Jia J; Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • Allers L; Department of Physics and Astronomy, The University of New Mexico, Albuquerque, NM, USA.
  • Wang F; Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • Mudd M; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • Timmins G; Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • Lidke K; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • Rusten TE; Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • Akepati PR; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • He Y; Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • Reggiori F; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • Eskelinen EL; Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • Deretic V; Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
EMBO J ; 42(14): e112845, 2023 07 17.
Article en En | MEDLINE | ID: mdl-37272163
ABSTRACT
The canonical autophagy pathway in mammalian cells sequesters diverse cytoplasmic cargo within the double membrane autophagosomes that eventually convert into degradative compartments via fusion with endolysosomal intermediates. Here, we report that autophagosomal membranes show permeability in cells lacking principal ATG8 proteins (mATG8s) and are unable to mature into autolysosomes. Using a combination of methods including a novel in vitro assay to measure membrane sealing, we uncovered a previously unappreciated function of mATG8s to maintain autophagosomal membranes in a sealed state. The mATG8 proteins GABARAP and LC3A bind to key ESCRT-I components contributing, along with other ESCRTs, to the integrity and imperviousness of autophagic membranes. Autophagic organelles in cells lacking mATG8s are permeant, are arrested as amphisomes, and do not progress to functional autolysosomes. Thus, autophagosomal organelles need to be maintained in a sealed state in order to become lytic autolysosomes.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Autofagia / Proteínas Asociadas a Microtúbulos Límite: Animals / Humans Idioma: En Revista: EMBO J Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Autofagia / Proteínas Asociadas a Microtúbulos Límite: Animals / Humans Idioma: En Revista: EMBO J Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos