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Mitochondrial phosphate-carrier deficiency: a novel disorder of oxidative phosphorylation.

ABSTRACT: The mitochondrial phosphate carrier SLC25A3 transports inorganic phosphate into the mitochondrial matrix, which is essential for the aerobic synthesis of adenosine triphosphate (ATP). We identified a homozygous mutation--c.215G-->A (p.Gly72Glu)--in the alternatively spliced exon 3A of this enzyme in two siblings with lactic acidosis, hypertrophic cardiomyopathy, and muscular hypotonia who died within the 1st year of life. Functional investigation of intact mitochondria showed a deficiency of ATP synthesis in muscle but not in fibroblasts, which correlated with the tissue-specific expression of exon 3A in muscle versus exon 3B in fibroblasts. The enzyme defect was confirmed by complementation analysis in yeast. This is the first report of patients with mitochondrial phosphate-carrier deficiency.

SUBMITTER: Mayr JA

PROVIDER: S-EPMC1821108 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature

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Mitochondrial phosphate-carrier deficiency: a novel disorder of oxidative phosphorylation.

Mayr Johannes A JA Merkel Olaf O Kohlwein Sepp D SD Gebhardt Boris R BR Böhles Hansjosef H Fötschl Ulrike U Koch Johannes J Jaksch Michaela M Lochmüller Hanns H Horváth Rita R Freisinger Peter P Sperl Wolfgang W

American journal of human genetics 20070110 3

The mitochondrial phosphate carrier SLC25A3 transports inorganic phosphate into the mitochondrial matrix, which is essential for the aerobic synthesis of adenosine triphosphate (ATP). We identified a homozygous mutation--c.215G-->A (p.Gly72Glu)--in the alternatively spliced exon 3A of this enzyme in two siblings with lactic acidosis, hypertrophic cardiomyopathy, and muscular hypotonia who died within the 1st year of life. Functional investigation of intact mitochondria showed a deficiency of ATP ...[more]

PMID: 17273968

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