Abnormalities of hydrogen sulfide and glutathione pathways in mitochondrial dysfunction

Mitochondrial disorders are genetic diseases for which therapy remains woefully inadequate. Therapy of these disorders is particularly challenging partially due to the heterogeneity and tissue-specificity of pathomechanisms involved in these disorders. Abnormalities in hydrogen sulfide (H₂S) metabolism are emerging as novel mechanism in mitochondrial dysfunction. However, further studies are necessary to understand the effects, protective or detrimental, of these abnormalities, and their relevance, in mitochondrial diseases.

To review the recent evidences of derangement of the metabolism of H₂S, at biosynthesis or oxidation levels, in mitochondrial dysfunction, focusing specifically on the alterations of H₂S oxidation caused by primary Coenzyme Q (CoQ) deficiency.

Mitochondria play a key role in the regulation of H₂S and GSH metabolism pathways. However, further studies are needed to understand the consequences of abnormalities of H₂S and GSH synthesis on the oxidation pathway, and vice versa; and on the levels of H₂S and GSH, their tissue-specific detrimental effects, and their role the role in mitochondrial diseases. Beside the known H₂S pathways, additional, tissue-specific, enzymatic systems, involved in H₂S production and elimination, might exist.