Exploring mitochondrial hydrogen sulfide signalling for therapeutic interventions in vascular diseases

Abstract

Hydrogen sulfide (H2S), a gaseous signalling molecule, is important in numerous physiological and pathophysiological processes. Despite its initial identification as an environmental toxin, H2S is now well described as an essential physiological molecule that is finely balanced to maintain cellular functions, especially in modulating mitochondrial activity. Mitochondria are responsible for the oxidation of H2S and its safe elimination while maintaining mitochondrial biogenesis. H2S oxidation in mitochondria generates various reactive sulfur species that could post-translationally modify proteins by sulfhydration. Sulfhydrated proteins participate in many regulatory activities either by direct interactions in the electron transport chain or indirect regulation by epigenetics. These investigations explain the importance of research of H2S as a therapeutic molecule beyond the traditional understanding as a protective role through its anti-inflammatory and antioxidant properties. This review focuses on highlighting the significant involvement of the H2S pathway in vascular diseases and current H2S donors for therapeutic use under development.