Impaired Mitochondrial Beta-oxidation in a Patient with an Abnormality of the Respiratory Chain. Studies in Skeletal Muscle Mitochondria

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1990 Jan 1

PMID 2153151

Citations 18

Authors

N J Watmough

L A Bindoff

M A Birch-Machin

S Jackson

K Bartlett

C I Ragan

J Poulton

R M Gardiner

H S Sherratt

D M Turnbull

Affiliations

Soon will be listed here.

Abstract

Defects of complex I of the mitochondrial respiratory chain are important causes of neurological disease. We report studies that demonstrate a severe deficiency of complex I activity with less severe abnormalities of complexes III and IV (less than 5, 63, and 30% of control values, respectively) in a skeletal muscle mitochondrial fraction from a 22-yr-old female with weakness, lactic acidemia, and the deposition of intramuscular neutral lipid. The observation that lipid accumulates in this and other patients with complex I deficiency suggests impaired mitochondrial fatty acid oxidation. To investigate this mechanism we have shown impaired flux through beta-oxidation [( U-14C]hexadecanoate oxidation was 66% of control rate) and accumulation of specific acyl-CoA ester intermediates. The changes in fatty acid metabolism in complex I deficiency are secondary to the reduced state within the mitochondrial matrix with low NAD+/NADH ratios.

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