Acetylation of the Mitochondrial Chaperone GRP75 Governs ER-Mitochondrial Calcium Homeostasis and Hepatocyte Insulin Resistance.

ABSTRACT: Overnutrition exacerbates insulin resistance (IR) and is linked to excessive mitochondrial protein acetylation. However, the molecular mechanism by which mitochondrial protein acetylation influences hepatic IR remains incompletely elucidated. To investigate this biology, GCN5L1 liver knockout mice (LKO), which exhibit blunted mitochondrial protein acetylation are utilized. Interestingly, the hepatocytes of LKO mice exhibit impaired insulin signaling and exaggerated endoplasmic reticulum (ER) stress. To explore putative mechanisms, protein-interaction and acetyl-proteome analyses are conducted following hepatic induction of GCN5L1. The mitochondrial chaperone GRP75 interacts with GCN5L1 and is acetylated on lysine residues K567 and K612 by GCN5L1 overexpression. Furthermore, GRP75-K567/612

SUBMITTER: Wang D 

PROVIDER: S-EPMC12697862 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature