H2S preconditioning induces long- lived perturbations in O2 metabolism

• 成果类型: Article
• 署名作者: Hanna, David A.; Diessl, Jutta; Guha, Arkajit; Kumar, Roshan; Andren, Anthony; Lyssiotis, Costas; Banerjee, Ruma
• 署名单位: University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10490
• DOI: 10.1073/pnas.2319473121
• 发表日期: 2024-03-19
• 关键词: hydrogen-sulfide oxidation; cytochrome-c-oxidase; animation-like state; reperfusion injury; nitric-oxide; mitochondrial; respiration; inhibition; mechanism; oxygen

摘要

Hydrogen sulfide exposure in moderate doses can induce profound but reversible hypometabolism in mammals. At a cellular level, H2S inhibits the electron transport chain (ETC), augments aerobic glycolysis, and glutamine- dependent carbon utilization via reductive carboxylation; however, the durability of these changes is unknown. We report that despite its volatility, H2S preconditioning increases P50(O2), the O2 pressure for half- maximal cellular respiration, and has pleiotropic effects on oxidative metabolism that persist up to 24 to 48 h later. Notably, cyanide, another complex IV inhibitor, does not induce this type of metabolic memory. Sulfide- mediated prolonged fractional inhibition of complex IV by H2S is modulated by sulfide quinone oxidoreductase, which commits sulfide to oxidative catabolism. Since induced hypometabolism can be beneficial in disease settings that involve insufficient or interrupted blood flow, our study has important implications for attenuating reperfusion- induced ischemic injury and/ or prolonging the shelf life of biologics like platelets.