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Significance Cu/Zn superoxide dismutase (Sod1) is a key antioxidant enzyme, and its importance is underscored by the fact that its ablation in cell and animal models results in oxidative stress; metabolic defects; and reductions in cell proliferation, viability, and lifespan. Curiously, Sod1 detoxifies superoxide radicals (O 2 •− ) in a manner that produces an oxidant as byproduct, hydrogen peroxide (H 2 O 2 ). While much is known about the necessity of scavenging O 2 •− , it is less clear what the physiological roles of Sod1-derived H 2 O 2 are. We discovered that Sod1-derived H 2 O 2 plays an important role in antioxidant defense by stimulating the production of NADPH, a vital cellular reductant required for reactive oxygen species scavenging enzymes, as well as redox regulating a large network of enzymes.
Montllor-Albalate et al. (Thu,) studied this question.