The potential role of hydrogen sulfide-autophagy axis in diseases.

Hydrogen sulfide (H2S), as a gaseous signaling molecule, assumes a pivotal role in regulating diverse physiological processes within cellular environments. Autophagy, a conserved intracellular degradation mechanism, is essential for maintaining cellular homeostasis through the removal of damaged organelles and misfolded proteins. Both H2S and autophagy display context-dependent dual roles—exerting either protective or detrimental effects depending on disease type, severity, and cellular environment. This review elucidates the intricate interplay between H2S and autophagy, focusing on their regulatory mechanisms and the impact they exert on inflammation, cancer, neurodegenerative diseases, ischemia-reperfusion injury, and metabolic disorders. We discuss how H2S modulates autophagy through signaling pathways that involve reactive oxygen species, endoplasmic reticulum stress, AMP-activated protein kinase, and the mechanistic target of rapamycin. Furthermore, we highlight the therapeutic potential of targeting the H2S-autophagy axis in the prevention and treatment of diseases. This review provides a theoretical foundation for future research that aims to harness the protective effects of H2S and autophagy while mitigating their adverse outcomes in pathological conditions.