Cystathionine γ lyase S-sulfhydrates Drp1 to ameliorate heart dysfunction.

ABSTRACT: Hydrogen sulfide (H₂S), produced by cystathionine γ lyase (CSE), is an important endogenous gasotransmitter to maintain heart function. However, the molecular mechanism for how H₂S influences the mitochondrial morphology during heart failure remains poorly understood. Here, we found that CSE/H₂S pathway mediated cardiac function and mitochondrial morphology through regulating dynamin related protein 1 (Drp1) activity and translocation. Mechanistically, elevation of H₂S levels by CSE overexpression declined protein level, phosphorylation (Ser 616), oligomerization and GTPase activity of Drp1 by S-sulfhydration in mouse hearts. Interestingly, Drp1 S-sulfhydration directly competed with S-nitrosylation by nitric oxide at the specific cysteine 607. T

SUBMITTER: Wu D 

PROVIDER: S-EPMC9626384 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature