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Sod1 integrates oxygen availability to redox regulate NADPH production and the thiol redoxome.

ABSTRACT: Cu/Zn superoxide dismutase (Sod1) is a highly conserved and abundant antioxidant enzyme that detoxifies superoxide (O₂ ^•-) by catalyzing its conversion to dioxygen (O₂) and hydrogen peroxide (H₂O₂). Using Saccharomyces cerevisiae and mammalian cells, we discovered that a major aspect of the antioxidant function of Sod1 is to integrate O₂ availability to promote NADPH production. The mechanism involves Sod1-derived H₂O₂ oxidatively inactivating the glycolytic enzyme, GAPDH, which in turn reroutes carbohydrate flux to the oxidative phase of the pentose phosphate pathway (oxPPP) to generate NADPH. The aerobic oxidation of GAPDH is dependent on and rate-limited by Sod1. Thus, Sod1 senses O₂ via O₂ ^•- to balance glycolytic and oxPPP flux, through control of GAPDH activity, for adaptation to life in air. Importantly, this mechanism for Sod1 antioxidant activity requires the bulk of cellular Sod1, unlike for its role in protection against O₂ ^•- toxicity, which only requires <1% of total Sod1. Using mass spectrometry, we identified proteome-wide targets of Sod1-dependent redox signaling, including numerous metabolic enzymes. Altogether, Sod1-derived H₂O₂ is important for antioxidant defense and a master regulator of metabolism and the thiol redoxome.

SUBMITTER: Montllor-Albalate C

PROVIDER: S-EPMC8740578 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Sod1 integrates oxygen availability to redox regulate NADPH production and the thiol redoxome.

Montllor-Albalate Claudia C Kim Hyojung H Thompson Anna E AE Jonke Alex P AP Torres Matthew P MP Reddi Amit R AR

Proceedings of the National Academy of Sciences of the United States of America 20220101 1

Cu/Zn superoxide dismutase (Sod1) is a highly conserved and abundant antioxidant enzyme that detoxifies superoxide (O2•-) by catalyzing its conversion to dioxygen (O2) and hydrogen peroxide (H2O2). Using Saccharomyces cerevisiae and mammalian cells, we discovered that a major aspect of the antioxidant function of Sod1 is to integrate O2 availability to promote NADPH production. The mechanism involves Sod1-derived H2</s ...[more]

PMID: 34969852

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Dataset Information

Sod1 integrates oxygen availability to redox regulate NADPH production and the thiol redoxome.

Publications

Sod1 integrates oxygen availability to redox regulate NADPH production and the thiol redoxome.

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