Background Wilson's disease (WD) is caused by mutations in a P-type ATPase
and is associated with copper deposition in liver and brain. The WD protein
is present in the trans-Golgi network and may also be imported into mitoch
ondria. The WD protein functions as a P-type copper transporting ATPase in
the Golgi but any action in mitochondria is at present unknown.
Methods We studied mitochondrial function and aconitase activity in WD live
r tissue and compared the results with those in a series of healthy control
s and patients without WD.
Findings There was evidence of severe mitochondrial dysfunction in the live
rs of patients with WD. Enzyme activities were decreased as follows: comple
x I by 62%, complex II+III by 52%, complex IV by 33%, and aconitase by 71%.
These defects did not seem to be secondary to penicillamine use, cholestas
is, or poor hepatocellular synthetic function,
Interpretation The results show that there is a defect of energy metabolism
in WD. The pattern of enzyme defects suggests that free-radical formation
and oxidative damage, probably mediated via mitochondrial copper accumulati
on, are important in WD pathogenesis, These results provide a rationale for
a study of the use of antioxidants in WD.