OBJECTIVE: The present study was aimed to know the contributions of mitochondrial respiratory chain enzymes to the development of liver failure and to the liver pathophysiology of metabolic liver diseases.
METHODS: We investigated the mitochondrial respiratory chain enzymes in liver samples obtained from 4 patients with liver failure due to unknown etiology and from 12 patients with metabolic diseases: ornithine transcarbamylase deficiency, 6 cases; Wilson disease, 3 cases; neonatal hemochromatosis, 2 cases. The estimation of mitochondrial respiratory chain enzymes was carried out by i) BN-PAGE in gel enzyme staining, ii) BN-PAGE western blotting, and iii) in vitro respiratory chain enzyme assay.
RESULTS: 4 cases with liver failure showed extremely low activities and protein levels of complex I, III, and IV. We also performed qPCR and estimated the ratio mtDNA/nDNA using these samples. They all exhibited extremely low ratio (2-7 %; normal is 60-150%), and were diagnosed as mtDNA depletion syndrome.
Mild or moderate decreases in enzyme activities were found in patients with metabolic liver disease, but the respective protein levels remained normal.
CONCLUSIONS: Mitochondrial respiratory chain defect might be an etiology of liver failure in a considerable number of patients in Japan. Secondary mitochondrial respiratory chain disorder is able to occur in metabolic liver disease in children.
