Exogenous Hydrogen Sulfide Plays an Important Role by Regulating Autophagy in Diabetic-Related Diseases

Abstract

Autophagy is a vital cell mechanism which plays an important role in many physiological processes including clearing long-lived, accumulated and misfolded proteins, removing damaged organelles and regulating growth and aging. Autophagy also participates in a variety of biological functions, such as development, cell differentiation, resistance to pathogens and nutritional hunger. Recently, autophagy has been reported to be involved in diabetes, but the mechanism is not fully understood. Hydrogen sulfide (H₂S) is a colorless, water-soluble, flammable gas with the typical odor of rotten eggs, which has been known as a highly toxic gas for many years. However, it has been reported recently that H₂S, together with nitric oxide and carbon monoxide, is an important gas signal transduction molecule. H₂S has been reported to play a protective role in many diabetes-related diseases, but the mechanism is not fully clear. Recent studies indicate that H₂S plays an important role by regulating autophagy in many diseases including cancer, tissue fibrosis diseases and glycometabolic diseases; however, the related mechanism has not been fully studied. In this review, we summarize recent research on the role of H₂S in regulating autophagy in diabetic-related diseases to provide references for future related research.

Keywords: autophagy; diabetes; hydrogen sulfide; oxidative stress; signaling pathway.

Figure 1

The general process of macroautophagy, microautophagy and chaperone-mediated autophagy. In the process of macroautophagy, the content is wrapped by a bilayer membrane structure to form an autophagosome and then fuses with lysosomes for degradation. Microautophagy refers to the process by which the lysosomal membranes directly invaginate and then encapsulate the cell contents. In the process of chaperone-mediated autophagy, the cytosolic proteins are transported to the lysosomal chamber after binding to molecular chaperones and then are digested by lysosomal enzymes.

Figure 2

Summary of the production process of endogenous H₂S. CBS: cystathionine-beta-synthase; CSE: cystathionine-gamma-lyase; 3-MST: 3-mercaptopyruvate thiotransferase; 3-MP: 3-mercaptopyruvate; CAT: cysteine aminotransferase.