Figure 2.

A new possibility of H₂S in anti-aging via mitohormesis. Mitohormesis refers to as an adaptive response through which the induction of mild or moderate mitochondrial stress can promote the viability and health of a cell, tissue, or organism. Depending on the severity of the perceived stress, there are varying hormetic responses existing in the mitochondria called mitochondrial stress response to adapt to different stress levels. The mitochondrial unfolded protein response (UPR^mt) is activated as the first line of defense for mitigating the stress, which induces a retrograde signaling pathway from the mitochondria to the nucleus, leading to the expression of proteases, chaperonins, and many stress response genes to degrade the unfolded or misfolded proteins and re-establish the mitochondrial protein homeostasis. In addition, mitochondria are highly dynamic organelles that undergo coordinated cycles of fission and fusion, referred to as mitochondrial dynamics, to maintain their size, shape, and distribution. When the stress level is increased, mitochondrial dynamics comes into action. When the mitochondrial stress level is overwhelmed, a selective type of autophagy targeting the damaged mitochondria for degradation, termed mitophagy, takes place. H₂S can be an important regulator for these mitochondrial stress responses, both directly and indirectly, as this gas itself may be a pro-oxidant by stimulating the Fenton reaction or it may undergo the sulfide oxidation pathway in the mitochondria to generate highly reactive sulfur species (RSS), which can be further oxidized or can modify cysteine residues via persulfidation.