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Zischka, H. ; Lichtmannegger, J.

Pathological mitochondrial copper overload in livers of Wilson's disease patients and related animal models.

Ann. NY Acad. Sci. 1315, 6-15 (2014)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
In Wilson's disease (WD) and related animal models, liver mitochondria are confronted with an increasing copper burden. Physiologically, the mitochondrial matrix may act as a dynamic copper buffer that efficiently distributes the metal to its copper-dependent enzymes. Mitochondria are the first responders in the event of an imbalanced copper homeostasis, as typical changes of their structure are among the earliest observable pathological features in WD. These changes are due to accumulating copper in the mitochondrial membranes and can be reversed by copper-chelating therapies. At the early stage, copper-dependent oxidative stress does not seem to occur. On the contrary, however, when copper is massively deposited in mitochondria, severe structural and respiratory impairments are observed upon disease progression. This provokes reactive oxygen species and consequently causes the mitochondrial membranes to disintegrate, which triggers hepatocyte death. Thus, in WD mitochondria are prime targets for copper, and the excessive copper burden causes their destruction, subsequently provoking tissue failure and death.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Wilson's Disease ; Copper ; Mitochondria ; Oxidative Stress; Evans Cinnamon Rats; Toxic Milk Mice; Oxidative Stress; Hepatic Copper; Hepatocellular Mitochondria; Intracellular Distribution; Permeability Transition; Superoxide-dismutase; Transporting Atpase; Reactive Oxygen
ISSN (print) / ISBN 0077-8923
e-ISSN 1749-6632
Journal Annals of the New York Academy of Sciences
Quellenangaben Volume: 1315, Issue: 1, Pages: 6-15 Article Number: , Supplement: ,
Publisher New York Academy of Sciences
Publishing Place Oxford
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Toxicology and Pharmacology (TOXI)