G protein β5-ATM complexes drive acetaminophen-induced hepatotoxicity.

ABSTRACT: Excessive ingestion of the common analgesic acetaminophen (APAP) leads to severe hepatotoxicity. Here we identify G protein β5 (Gβ₅), elevated in livers from APAP overdose patients, as a critical regulator of cell death pathways and autophagic signaling in APAP-exposed liver. Liver-specific knockdown of Gβ₅ in mice protected the liver from APAP-dependent fibrosis, cell loss, oxidative stress, and inflammation following either acute or chronic APAP administration. Conversely, overexpression of Gβ₅ in liver was sufficient to drive hepatocyte dysfunction and loss. In hepatocytes, Gβ₅ depletion ameliorated mitochondrial dysfunction, allowed for maintenance of ATP generation and mitigated APAP-induced cell death. Further, Gβ₅ knockdown also

SUBMITTER: Pramanick A 

PROVIDER: S-EPMC8105674 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature