title: SOD1 integrates signals from oxygen and glucose to repress respiration.
abstract: Cu/Zn superoxide dismutase (SOD1) is an abundant enzyme that has been best studied as a regulator of antioxidant defense. Using the yeast Saccharomyces cerevisiae, we report that SOD1 transmits signals from oxygen and glucose to repress respiration. The mechanism involves SOD1-mediated stabilization of two casein kinase 1-gamma (CK1γ) homologs, Yck1p and Yck2p, required for respiratory repression. SOD1 binds a C-terminal degron we identified in Yck1p/Yck2p and promotes kinase stability by catalyzing superoxide conversion to peroxide. The effects of SOD1 on CK1γ stability are also observed with mammalian SOD1 and CK1γ and in a human cell line. Therefore, in a single circuit, oxygen, glucose, and reactive oxygen can repress respiration through SOD1/CK1γ signaling. Our data therefore may provide mechanistic insight into how rapidly proliferating cells and many cancers accomplish glucose-mediated repression of respiration in favor of aerobic glycolysis.
authors: Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA.
authors: Amit R
authors: AR
authors: Reddi
authors: Valeria C
authors: VC
authors: Culotta
mesh_terms: D000595:Amino Acid Sequence; D047389:Casein Kinase I / Q000378:metabolism; D002460:Cell Line; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008969:Molecular Sequence Data; D010100:Oxygen / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D013481:Superoxides / Q000378:metabolism
chemical_list: C000606290:SOD1 protein, human; D029701:Saccharomyces cerevisiae Proteins; D013481:Superoxides; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D047389:Casein Kinase I; C479664:YCK1 protein, S cerevisiae; D005947:Glucose; D010100:Oxygen