Hydrogen Sulfide, an Endogenous Stimulator of Mitochondrial Function in Cancer Cells

Hydrogen sulfide (H2S) has a long history as toxic gas and environmental hazard; inhibition of cytochrome c oxidase (mitochondrial Complex IV) is viewed as a primary mode of its cytotoxic action. However, studies conducted over the last two decades unveiled multiple biological regulatory roles of H2S as an endogenously produced mammalian gaseous transmitter. Cystathionine gamma-lyase (CSE), cystathionine beta-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST) are currently viewed as the principal mammalian H2S-generating enzymes. In contrast to its inhibitory (toxicological) mitochondrial effects, at lower (physiological) concentrations, H2S serves as a stimulator of electron transport in mammalian mitochondria, by acting as an electron donor-with sulfide:quinone oxidoreductase (SQR) being the immediate electron acceptor. The mitochondrial roles of H2S are significant in various cancer cells, many of which exhibit high expression and partial mitochondrial localization of various H2S producing enzymes. In addition to the stimulation of mitochondrial ATP production, the roles of endogenous H2S in cancer cells include the maintenance of mitochondrial organization (protection against mitochondrial fission) and the maintenance of mitochondrial DNA repair (via the stimulation of the assembly of mitochondrial DNA repair complexes). The current article overviews the state-of-the-art knowledge regarding the mitochondrial functions of endogenously produced H2S in cancer cells.

Automated summary

H2S, previously known as a toxic gas and environmental hazard, has been found to play multiple biological regulatory roles in mammalian cells as an endogenously produced gaseous transmitter. Its effects in mitochondria serve as an electron transport stimulator in physiological concentrations, particularly significant in cancer cells where it helps maintain mitochondrial organization and DNA repair.