The mitochondrial calcium uniporter mediates mitochondrial Fe²⁺ uptake and hepatotoxicity after acetaminophen.

ABSTRACT: Acetaminophen (APAP) overdose disrupts hepatocellular lysosomes, which release ferrous iron (Fe²⁺) that translocates into mitochondria putatively via the mitochondrial calcium uniporter (MCU) to induce oxidative/nitrative stress, the mitochondrial permeability transition (MPT), and hepatotoxicity. To investigate how MCU deficiency affects mitochondrial Fe²⁺ uptake and hepatotoxicity after APAP overdose, global MCU knockout (KO), hepatocyte specific (hs) MCU KO, and wildtype (WT) mice were treated with an overdose of APAP both in vivo and in vitro. Compared to strain-specific WT mice, serum ALT decreased by 88 and 56%, respectively, in global and hsMCU KO mice at 24 h after APAP (300 mg/kg). Hepatic necrosis also decreased by 84 and 56%. By contrast, when MCU was knock

SUBMITTER: Hu J 

PROVIDER: S-EPMC10872750 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature