Glutaredoxin attenuates glutathione levels via deglutathionylation of Otub1 and subsequent destabilization of system x_C.

ABSTRACT: Glutathione (GSH) is a critical component of the cellular redox system that combats oxidative stress. The glutamate-cystine antiporter, system x_C^-, is a key player in GSH synthesis that allows for the uptake of cystine, the rate-limiting building block of GSH. It is unclear whether GSH or GSH-dependent protein oxidation [protein S-glutathionylation (PSSG)] regulates the activity of system x_C^-. We demonstrate that an environment of enhanced PSSG promotes GSH increases via a system x_C^--dependent mechanism. Absence of the deglutathionylase, glutaredoxin (GLRX), augmented SLC7A11 protein and led to significant increases of GSH content. S-glutathionylation of C23 or C204 of the deubiquitinase OTUB1 promoted interact

SUBMITTER: Aboushousha R 

PROVIDER: S-EPMC10499329 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature