Publication:

Mitochondrial phosphate-carrier deficiency: a novel disorder of oxidative phosphorylation (2007)

Author(s): Mayr JA; Merkel O; Kohlwein SD; Gebhardt BR; Bohles H; Fotschl U; Koch J; Jaksch M; Lochmuller H; Horvath R; Freisinger P; Sperl W

    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.

    • Type of Article: Report
    • Date: 11-12-2006
    • Journal: American Journal of Human Genetics
    • Volume: 80
    • Issue: 3
    • Pages: 478-484
    • Publisher: Cell Press
    • Publication type: Article
    • Bibliographic status: Published

    Keywords: Acidosis, Lactic/complications/metabolism Adenosine Triphosphate/metabolism Alternative Splicing Amino Acid Sequence Cardiomyopathy, Hypertrophic/complications/metabolism Cells, Cultured Energy Metabolism Exons/genetics Female Fibroblasts/metabolism Genetic Complementation Test Homozygote Humans Infant Infant, Newborn Male Mitochondria, Heart/ metabolism Mitochondria, Muscle/ metabolism Mitochondrial Proteins/ deficiency/genetics Molecular Sequence Data Muscle Hypotonia/complications/metabolism Mutation/ genetics Oxidative Phosphorylation Pedigree Phosphate Transport Proteins/ deficiency/genetics Phosphates/ metabolism Saccharomyces cerevisiae/genetics/growth & development/metabolism Sequence Homology, Amino Acid Siblings

    Staff

    Dr Rita Horvath
    Senior Lecturer/Honorary Consultant

    Professor Hanns Lochmuller
    Professor of Experimental Myology