title: Kearns-Sayre syndrome: biochemical studies of mitochondrial metabolism.
abstract: 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.
authors.affiliation: Department of Neurology, Wayne State University School of Medicine, Detroit, MI 48201.
authors.forename: M E
authors.initials: ME
authors.lastname: Martens
authors.forename: P L
authors.initials: PL
authors.lastname: Peterson
authors.forename: C P
authors.initials: CP
authors.lastname: Lee
authors.forename: M A
authors.initials: MA
authors.lastname: Nigro
authors.forename: Z
authors.initials: Z
authors.lastname: Hart
authors.forename: M
authors.initials: M
authors.lastname: Glasberg
authors.forename: J S
authors.initials: JS
authors.lastname: Hatfield
authors.forename: C H
authors.initials: CH
authors.lastname: Chang
mesh_terms: 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
chemical_list: D014451:Ubiquinone; D003576:Electron Transport Complex IV