SOD1 is an essential H₂S detoxifying enzyme

Area of Science:

• Biochemistry
• Cellular Biology
• Toxicology

Background:

• Hydrogen sulfide (H2S) is an endogenous signaling molecule with dual roles: antioxidant and cytotoxic.
• H2S inhibits mitochondrial respiration by targeting cytochrome c oxidase.
• Current understanding suggests H2S detoxification occurs slowly within the mitochondrial matrix, posing a paradox given its rapid cytotoxicity.

Purpose of the Study:

• To identify cellular mechanisms for rapid hydrogen sulfide (H2S) detoxification.
• To investigate the role of superoxide dismutase [Cu-Zn] (SOD1) in H2S metabolism and toxicity.

Main Methods:

• Assessing H2S detoxification efficiency by SOD1 under varying sulfide concentrations.
• Evaluating the impact of altered SOD1 expression (decreased and increased) on cellular H2S sensitivity in yeast and human cells.
• Measuring reactive oxygen species (ROS) levels in SOD1-deficient cells exposed to sulfide.

Main Results:

• Superoxide dismutase [Cu-Zn] (SOD1) demonstrates efficient H2S oxidase activity, converting H2S to sulfate.
• Reduced SOD1 expression increases sensitivity to H2S toxicity, while enhanced SOD1 expression confers tolerance.
• Under high sulfide conditions, SOD1 catalyzes per- and polysulfide formation, inducing thiol oxidation.
• SOD1-deficient cells exhibit elevated ROS, which can also oxidize sulfide to per- and polysulfides.

Conclusions:

• SOD1 plays a fundamental role in detoxifying hydrogen sulfide (H2S).
• SOD1 regulates both H2S levels and the formation of related reactive sulfur species.
• This study uncovers a critical function for SOD1 in mitigating H2S-induced cellular damage.