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

SUBMITTER: Montllor-Albalate C 

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

REPOSITORIES: biostudies-literature