Kearns‐sayre syndrome: Biochemical studies of mitochondrial metabolism

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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 Decemberreased, 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.