A point mutation in the cytb gene of cardiac mtDNA associated with complex III deficiency in ischemic cardiomyopathy.
We report a high incidence of reduced respiratory Complex III activity in heart muscle concomitant with the presence of a specific mutation in cytochrome b (cytb) in patients with ischemic cardiomyopathy. This C-->A mutation at nt 15452 converts the 236th residue of cytb from a leucine to isoleucine, is heteroplasmic and was observed in only 2 of 43 controls. Complex III activity is reduced (> 50%) in 5 of 6 patients with the C-->A15452 mutation suggesting that the cytb mutation is responsible for decreased Complex III activity and may play a role in the pathophysiology of ischemic cardiomyopathy.
Molecular Cardiology Institute, Highland Park, NJ 08904, USA.
J
J
Marin-Garcia
Y
Y
Hu
R
R
Ananthakrishnan
M E
ME
Pierpont
G L
GL
Pierpont
M J
MJ
Goldenthal
D000328:Adult; D000368:Aged; D003573:Cytochrome b Group / Q000235:genetics*; D030401:Cytochrome-c Oxidase Deficiency; D004272:DNA, Mitochondrial / Q000235:genetics*; D014450:Electron Transport Complex III / Q000172:deficiency* / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000201:enzymology / Q000235:genetics; D017202:Myocardial Ischemia / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000172:deficiency / Q000378:metabolism; D017354:Point Mutation; D016133:Polymerase Chain Reaction
D003573:Cytochrome b Group; D004272:DNA, Mitochondrial; D016660:NAD(P)H Dehydrogenase (Quinone); D003576:Electron Transport Complex IV; D014450:Electron Transport Complex III