Liver mitochondrial membrane crosslinking and destruction in a rat model of Wilson disease.

ABSTRACT: Wilson disease (WD) is a rare hereditary condition that is caused by a genetic defect in the copper-transporting ATPase ATP7B that results in hepatic copper accumulation and lethal liver failure. The present study focuses on the structural mitochondrial alterations that precede clinical symptoms in the livers of rats lacking Atp7b, an animal model for WD. Liver mitochondria from these Atp7b–/– rats contained enlarged cristae and widened intermembrane spaces, which coincided with a massive mitochondrial accumulation of copper. These changes, however, preceded detectable deficits in oxidative phosphorylation and biochemical signs of oxidative damage, suggesting that the ultrastructural modifications were not the result of oxidative stress imposed by copper- dependent Fenton chemistry. In a c

SUBMITTER: Zischka H 

PROVIDER: S-EPMC3068979 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature