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Stress granules and mTOR are regulated by membrane atg8ylation during lysosomal damage.
Jia, Jingyue; Wang, Fulong; Bhujabal, Zambarlal; Peters, Ryan; Mudd, Michal; Duque, Thabata; Allers, Lee; Javed, Ruheena; Salemi, Michelle; Behrends, Christian; Phinney, Brett; Johansen, Terje; Deretic, Vojo.
  • Jia J; Autophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, Albuquerque, NM.
  • Wang F; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM.
  • Bhujabal Z; Autophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, Albuquerque, NM.
  • Peters R; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM.
  • Mudd M; Autophagy Research Group, Institute of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway.
  • Duque T; Autophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, Albuquerque, NM.
  • Allers L; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM.
  • Javed R; Autophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, Albuquerque, NM.
  • Salemi M; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM.
  • Behrends C; Autophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, Albuquerque, NM.
  • Phinney B; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM.
  • Johansen T; Autophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, Albuquerque, NM.
  • Deretic V; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM.
J Cell Biol ; 221(11)2022 11 07.
Article in English | MEDLINE | ID: covidwho-2051188
ABSTRACT
We report that lysosomal damage is a hitherto unknown inducer of stress granule (SG) formation and that the process termed membrane atg8ylation coordinates SG formation with mTOR inactivation during lysosomal stress. SGs were induced by lysosome-damaging agents including SARS-CoV-2ORF3a, Mycobacterium tuberculosis, and proteopathic tau. During damage, mammalian ATG8s directly interacted with the core SG proteins NUFIP2 and G3BP1. Atg8ylation was needed for their recruitment to damaged lysosomes independently of SG condensates whereupon NUFIP2 contributed to mTOR inactivation via the Ragulator-RagA/B complex. Thus, cells employ membrane atg8ylation to control and coordinate SG and mTOR responses to lysosomal damage.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: DNA Helicases / RNA Helicases / Autophagy-Related Protein 8 Family Limits: Animals Language: English Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: DNA Helicases / RNA Helicases / Autophagy-Related Protein 8 Family Limits: Animals Language: English Year: 2022 Document Type: Article