INTRINSIC UNCOUPLING OF CYTOCHROME-C-OXIDASE MAY CAUSE THE MATERNALLYINHERITED MITOCHONDRIAL DISEASES MELAS AND LHON

Mutations in the human mtDNA gene encoding subunit LU of cytochrome c oxidase (CO) have been reported to cause MELAS and LHON. Paracoccus de nitrificans cells expressing substitutions homologous to these MELAS- and LHON-causing mutations had lower growth yield than wild type cells and lower efficiency of proton pumping by CO (e.g, lower H+/e(-) rati o and lower Delta Psi), but had similar CO activity. These results ind icate that both substitutions (F263L > A212T) cause intrinsic uncoupli ng, which may be the direct cause of the diseases. These results also suggest that subunit III is involved in proton pumping. (C) 1998 Feder ation of European Biochemical Societies.