title: Stress granules inhibit apoptosis by reducing reactive oxygen species production.
abstract: Cells can undergo two alternative fates following exposure to environmental stress: they either induce apoptosis or inhibit apoptosis and then repair the stress-induced alterations. These processes minimize cell loss and prevent the survival of cells with aberrant DNA and protein alterations. These two alternative fates are partly controlled by stress granules (SGs). While arsenite, hypoxia, and heat shock induce the formation of SGs that inhibit apoptosis, X-ray irradiation and genotoxic drugs do not induce SGs, and they are more prone to trigger apoptosis. However, it is unclear precisely how SGs control apoptosis. This study found that SGs suppress the elevation of reactive oxygen species (ROS), and this suppression is essential for inhibiting ROS-dependent apoptosis. This antioxidant activity of SGs is controlled by two SG components, GTPase-activating protein SH3 domain binding protein 1 (G3BP1) and ubiquitin-specific protease 10 (USP10). G3BP1 elevates the steady-state ROS level by inhibiting the antioxidant activity of USP10. However, following exposure to arsenite, G3BP1 and USP10 induce the formation of SGs, which uncovers the antioxidant activity of USP10. We also found that the antioxidant activity of USP10 requires the protein kinase activity of ataxia telangiectasia mutated (ATM). This work reveals that SGs are critical redox regulators that control cell fate under stress conditions.
authors.affiliation: Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Masaya
authors.initials: M
authors.lastname: Higuchi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Matsuki
authors.forename: Manami
authors.initials: M
authors.lastname: Yoshita
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Ohsawa
authors.forename: Masayasu
authors.initials: M
authors.lastname: Oie
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujii
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D018053:Arsenites / Q000633:toxicity; D064007:Ataxia Telangiectasia Mutated Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D003594:Cytoplasmic Granules / Q000378:metabolism*; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress; D039122:Poly(A)-Binding Protein I / Q000378:metabolism; D000075223:Poly-ADP-Ribose Binding Proteins; D025941:Protein Interaction Mapping; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D020365:RNA Helicases; D034622:RNA Interference; D000067776:RNA Recognition Motif Proteins; D017382:Reactive Oxygen Species / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D018053:Arsenites; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D039122:Poly(A)-Binding Protein I; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D017382:Reactive Oxygen Species; D025521:Tumor Suppressor Proteins; C431363:USP10 protein, human; C579090:USP10 protein, mouse; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases; D043222:Ubiquitin Thiolesterase; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases; C015001:arsenite