Changes in mitochondrial complex I activity and coenzyme Q binding site in Leber's hereditary optic neuropathy (LHON).
The complex I function in sub-mitochondrial particles was studied in platelets from patients and healthy carriers with 11778/ND4 or 3460/ND1 mtDNA point mutations associated with LHON. Both 11778/ND4 and 3460/ND1 mutations induced rotenone resistance and 11778/ND4 showed an increased K(m) for ubiquinol-2 with respect to the control group. It was concluded that even with different pathogenic mechanisms both mutations affect the quinone binding site of complex I.
Ghelli
A
A
Department of Biochemistry G. Moruzzi, University of Bologna, Italy.
Degli Esposti
M
M
Carelli
V
V
Lenaz
G
G
D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D008928:Mitochondria / Q000378:metabolism*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D015418:Optic Atrophies, Hereditary / Q000378:metabolism*; D017354:Point Mutation; D012402:Rotenone / Q000494:pharmacology; D014451:Ubiquinone / Q000097:blood*; D014475:Uncoupling Agents / Q000494:pharmacology
D004272:DNA, Mitochondrial; D014475:Uncoupling Agents; D012402:Rotenone; D014451:Ubiquinone; D016660:NAD(P)H Dehydrogenase (Quinone); C025204:Ubiquinone Q2