MtDNA depletion-like syndrome in Wilson disease.

ABSTRACT:

Background and aims

Wilson disease (WD) is caused by mutations in the copper transporter ATP7B, with its main pathology attributed to copper-mediated oxidative damage. The limited therapeutic effect of copper chelators and the early occurrence of mitochondrial deficits, however, undermine the prevalence of this mechanism.

Methods

We characterized mitochondrial DNA copy number and mutations as well as bioenergetic deficits in blood from patients with WD and in livers of tx-j mice, a mouse model of hepatic copper accumulation. In vitro experiments with hepatocytes treated with CuSO₄ were conducted to validate in vivo studies.

Results

Here, for the first time, we characterized the bioenergetic deficits in WD as consistent with a mitochondrial DNA depletion-lik

SUBMITTER: Medici V 

PROVIDER: S-EPMC8079140 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature