Figure 8.

Summary of the various effects of H₂S on mitochondrial bioenergetics. (a) The novel findings contained in the current report (S-sulfhydration of ATP synthase) are indicated with red arrows. H₂S can be produced in the mitochondrion constitutively by two distinct H₂S-producing enzymes, 3-MST, and CBS. Moreover, CSE is capable of translocating to the mitochondrial outer membrane under certain stress condition (e.g.: increased intracellular calcium signal), contributing the growth of intramitochondrial H₂S level. Lower concentrations of H₂S exert stimulatory effects on mitochondrial function via several different mechanisms: (b) H₂S can donate electrons to mitochondrial electron transport chain. (c) H₂S can act as an antioxidant neutralizing mitochondrial-derived reactive oxygen and nitrogen species, stabilizing the electron transport chain proteins, as well as preventing mitochondrial DNA damage. (d) H₂S oxidization can results in sulfite, sulfate and thiosulfate; some of these species can also act as “pools” or sources of biologically active H₂S. (e) H₂S can inhibit mitochondrial PDE2A enzyme, which increases intramitochondrial cAMP levels, and stimulates mitochondrial function via activation of the cAMP-dependent protein kinase (PKA). Higher concentrations of H₂S can also exert marked inhibitory effects on mitochondrial function: (f) H₂S can inhibits cytochrome c oxidase (complex IV) resulting in a reversible inhibition of mitochondrial electron transport and ATP production.