Kearns-Sayre syndrome: biochemical studies of mitochondrial metabolism.
Examination of oxidative metabolism in mitochondria isolated from quadriceps skeletal muscle biopsy specimens of 4 patients with Kearns-Sayre syndrome has shown that the mitochondria were tightly coupled, with maximal respiratory rates depending on the presence of adenosine diphosphate (ADP), Ca2+, or uncoupler. The state 3 respiratory rates with nicotinamide adenine dinucleotide (NAD)-linked substrates and succinate were much lower than those of control subjects. The cytochrome oxidase activities (measured with ascorbate + phenazine methosulfate as substrates) were also decreased, but this segment of the respiratory chain was not rate-limiting for succinate or NAD-linked substrate oxidation. Analyses of the steady-state reduction kinetics of the respiratory chain carriers revealed that the rate-limiting step of the impaired respiration with succinate or NAD-linked substrates lies between the c cytochromes and cytochrome oxidase. Measurement of the total substrate-reducible (at anaerobiosis) and chemically reducible levels of the cytochromes in mitochondria from 3 patients showed a severe deficiency of cytochrome a + a3 and an excess of the c cytochromes. To our knowledge, this is the first instance in which a mitochondrial electron transfer defect and cytochrome oxidase deficiency has been shown to be associated with an excess of the c cytochromes.
Martens
M E
ME
Department of Neurology, Wayne State University School of Medicine, Detroit, MI 48201.
Peterson
P L
PL
Lee
C P
CP
Nigro
M A
MA
Hart
Z
Z
Glasberg
M
M
Hatfield
J S
JS
Chang
C H
CH
D000293:Adolescent; D000328:Adult; D002648:Child; D003576:Electron Transport Complex IV / Q000378:metabolism; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D007625:Kearns-Sayre Syndrome / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism* / Q000648:ultrastructure; D009886:Ophthalmoplegia / Q000378:metabolism*; D010101:Oxygen Consumption; D013379:Substrate Specificity; D014451:Ubiquinone / Q000378:metabolism
D014451:Ubiquinone; D003576:Electron Transport Complex IV