Hydrogen sulfide and autophagy: A double edged sword.

Hydrogen sulfide (HS) has been considered the third gaseous signaling molecule that plays important roles in a wide range of physiological and pathological conditions. However, there has been some controversy on the role of HS in autophagy. Recent studies indicate that a number of signaling pathways are involved in the pro-autophagy effect of HS, such as PI3K/Akt/mTOR, AMPK/mTOR, LKB1/STRAD/MO25, and miR-30c signaling pathways. On the other hand, there are many signaling pathways that play important roles in the anti-autophagy effect of HS, including SR-A, PI3K/SGK1/GSK3β, PI3K/AKT/mTOR, Nrf2-ROS-AMPK, AMPK/mTOR, and JNK1 signaling pathways. Novel HS-releasing donors/drugs could be designed and identified in order to increase the therapeutic effects by mediating autophagy in human diseases. In this review, the HS metabolism in mammals is summarized and the effects of signaling pathways in HS-mediated autophagy are further discussed.