Regulation of Autophagy by Hydrogen Sulfide

Abstract

Hydrogen sulfide has been considered a toxic molecule; however, it has also been recently recognized as a signaling molecule of comparable importance to NO and H₂O₂ in plants, where it mediates the tolerance response and regulates essential processes such as autophagy. Autophagy is a conserved mechanism with a pro-survival role, involving the sequestration of cytoplasmic constituents within structures called autophagosomes that are then targeted for degradation inside the vacuole. The essential components of autophagy are conserved; one such protein is ATG8, which has been extensively used to monitor autophagic activity in plants by immunoblotting analysis and GFP fluorescence detection.

The endogenous production of hydrogen sulfide occurs through the action of enzymes involved in the metabolism of cysteine. In plants, the chloroplast is the main source of sulfide; however, at the basic pH found within the stroma, sulfide cannot be transported outside the chloroplastic membrane. Thus, sulfide is metabolically generated in the cytosol; in Arabidopsis, the l-cysteine desulfhydrase, DES1, has been demonstrated to be responsible for sulfide production. Recent research has shown that sulfide behaves as a signaling molecule, acting as a repressor of autophagy. However, the underlying mechanism and the specific molecular targets are not well known, although two mechanisms have been proposed. The first mechanism relates to the nucleophilic properties of this molecule, in which sulfide acts as an antioxidant with reactive oxygen species as its molecular targets. The second mechanism, S-sulfhydration, consists of a posttranslational modification to thiol groups of cysteines within proteins to form persulfide groups. In plants, the action of sulfide through the endogenous S-sulfhydration of proteins has already been demonstrated, and different autophagic proteins can be hypothesized as targets for sulfide.