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Diagnostic Value of Succinate Ubiquinone Reductase Activity in the Identification of Patients with Mitochondrial DNA Depletion
Author(s) -
Hargreaves I. P.,
Rahman S.,
Guthrie P.,
Taanman JW.,
Leonard J. V.,
Land J. M.,
Heales S. J. R.
Publication year - 2002
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1023/a:1015104910239
Subject(s) - coenzyme q – cytochrome c reductase , reductase , cytochrome c oxidase , mitochondrial dna , biology , biochemistry , mitochondrion , succinate dehydrogenase , nuclear dna , ubiquinol , enzyme , microbiology and biotechnology , cytochrome c , gene
Abstract Mitochondrial DNA (mtDNA) depletion syndrome (McKusick 251880) is characterized by a progressive quantitative loss of mtDNA resulting in severe mitochondrial dysfunction. A diagnosis of mtDNA depletion can only be confirmed after Southern blot analysis of affected tissue. Only a limited number of centres have the facilities to offer this service, and this is frequently on an irregular basis. There is therefore a need for a test that can refine sample selection as well as complementing the molecular analysis. In this study we compared the activities of the nuclear‐encoded succinate ubiquinone reductase (complex II) to the activities of the combined mitochondrial and nuclear‐encoded mitochondrial electron transport chain (ETC) complexes; NADH:ubiquinone reductase (complex I), ubiquinol‐cytochrome‐ c reductase (complex III), and cytochrome‐ c oxidase (complex IV), in skeletal muscle biopsies from 7 patients with confirmed mtDNA depletion. In one patient there was no evidence of an ETC defect. However, the remaining 6 patients exhibited reduced complex I and IV activities. Five of these patients also displayed reduced complex II[ndash]III (succinate:cytochrome‐ c reductase) activity. Individual measurement of complex II and complex III activities demonstrated normal levels of complex II activity compared to complex III, which was reduced in the 5 biopsies assayed. These findings suggest a possible diagnostic value for the detection of normal levels of complex II activity in conjunction with reduced complex I, III and IV activity in the identification of likely candidates for mtDNA depletion syndrome