Fig. 2.
Restortion of mitochondrial ATP synthesis pathways by ischemia and H2S in muscle. Dietary L-homocysteine undergoes a reverse transsulfuration reaction by CBS, CSE, and 3-MST to produce endogenous H2S. Ischemia reduces expression of these enzymes, resulting in decreased endogenous H2S production. Introduction of an exogenous H2S donor (NaHS) can increase expression of the enzymes, resulting in increased endogenous H2S synthesis. This affects mitochondria by increasing KATP activity through increased gene expression of SUR2A-Kir6.1 and/or acting through UCP-2. This leads to increased Ca2+ export form the mitochondria, stimulating ATP transport. H2S also upregulates cAMP by inhibiting PDE2A, resulting in increased mitochondrial PKA activity to stimulate the electron transport chain (ETC), resulting in increased oxygen utilization and ATP production