Functional respiratory chain studies in subjects with chronic progressive external ophthalmoplegia and large heteroplasmic mitochondrial DNA deletions.
The functional consequences of large heteroplasmic mtDNA deletions were investigated in a group of 6 patients with chronic progressive external ophthalmoplegia (CPEO) syndromes. State III respiration rates corrected for age were low with site I and II substrates in all cases and cytochrome oxidase activity was depressed. The severity of impairment varied and is consistent with inclusion of a variable percentage of non-functioning mitochondria (with deleted mtDNA) in the pellet. Western blot studies with a holocomplex antibody battery revealed no abnormalities in subunit content of complexes III and IV. A deficiency of several complex I subunits in 3 cases suggests that abnormal nuclear-mitochondrial regulation of complex I assembly may follow large mtDNA deletions.
Trounce
I
I
Mitochondrial Diseases Investigational Unit, St. Vincent's Hospital, Fitzroy, Australia.
Byrne
E
E
Marzuki
S
S
Dennett
X
X
Sudoyo
H
H
Mastaglia
F
F
Berkovic
S F
SF
D000328:Adult; D002872:Chromosome Deletion; D030401:Cytochrome-c Oxidase Deficiency; D004272:DNA, Mitochondrial / Q000235:genetics*; D004579:Electron Transport; D014450:Electron Transport Complex III / Q000172:deficiency* / Q000235:genetics; D003576:Electron Transport Complex IV / Q000235:genetics; D005260:Female; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone); D009886:Ophthalmoplegia / Q000235:genetics / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D011808:Quinone Reductases / Q000172:deficiency* / Q000235:genetics; D012343:RNA, Transfer / Q000235:genetics; D013386:Succinates / Q000378:metabolism; D019802:Succinic Acid
D004272:DNA, Mitochondrial; D005971:Glutamates; D011773:Pyruvates; D013386:Succinates; D018698:Glutamic Acid; D019289:Pyruvic Acid; D012343:RNA, Transfer; D019802:Succinic Acid; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases; D003576:Electron Transport Complex IV; D014450:Electron Transport Complex III