ArticleLiver international : official journal of the International Association for the Study of the Liver2020
mtDNA depletion-like syndrome in Wilson disease.
Article in Liver international : official journal of the International Association for the Study of the Liver, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Mitochondrial dysfunction in Wilson disease: a systematic review and meta-analysis across human and animal models.Frontiers in molecular biosciences · 2025Pooled it
- The Role of Metal Ions in Mitochondria: From Energy Metabolism to Cell Destiny.Biological trace element research · 2026Review
- Sex-specific mitochondrial dysregulation and metformin response in Wilson disease.Scientific reports · 2026Article
- The pathogenesis of liver fibrosis in Wilson's disease: hepatocyte injury and regulation mediated by copper metabolism dysregulation.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Inactivation of Atp7b Copper Transporter in Intestinal Epithelial Cells Is Associated with Altered Lipid Processing and Cell Growth Machinery Independent from Hepatic Copper Accumulation and Severity of Liver Histology.The American journal of pathology · 2026Article
- The gut-liver-kidney-brain axis in Wilson disease: copper speciation-flux and barrier-mediated organ crosstalk.Frontiers in immunology · 2026Review
- IL-6 trans-Signaling Regulates Neutrophilic Inflammation in Alcohol-Associated Hepatitis.The American journal of pathology · 2026Article
- Discovery of newborn Wilson disease biomarkers via integrated next-generation sequencing and untargeted metabolomics.Orphanet journal of rare diseases · 2025Article
- Excess copper exposure and male reproductive toxicity: molecular mechanisms and potential interventions.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025Review
- Copper homeostasis and cuproptosis in Alzheimer's disease (Review).International journal of molecular medicine · 2025Review
- Uncovering the Critical Role of Cuproptosis in Wilson Disease: Insights Into Potential Therapeutic Targets.Journal of cellular and molecular medicine · 2025Article
- Role ofJournal of thoracic disease · 2025Article
- Mitochondrial dysfunction: A promising therapeutic target for liver diseases.Genes & diseases · 2024Review
- Mitochondrial copper in human genetic disorders.Trends in endocrinology and metabolism: TEM · 2023Review
- Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 4 countries.
Funding
Abstract
BACKGROUND AND
aimsWilson 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.
methodsWe 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 CuSO
resultsHere, for the first time, we characterized the bioenergetic deficits in WD as consistent with a mitochondrial DNA depletion-like syndrome. This is evidenced by enriched DNA synthesis/replication pathways in serum metabolomics and decreased mitochondrial DNA copy number in blood of WD patients as well as decreased mitochondrial DNA copy number, increased citrate synthase activity, and selective Complex IV deficit in livers of the tx-j mouse model of WD. Tx-j mice treated with the copper chelator penicillamine, methyl donor choline or both ameliorated mitochondrial DNA damage but further decreased mitochondrial DNA copy number. Experiments with copper-loaded HepG2 cells validated the concept of a direct copper-mitochondrial DNA interaction.
conclusionsThis study underlines the relevance of targeting the copper-mitochondrial DNA pool in the treatment of WD separate from the established copper-induced oxidative stress-mediated damage.
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Registered trials
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