title: 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.
authors.affiliation: Department of Pediatrics, Paracelsus Private Medical University, Salzburg, Austria. h.mayr@salk.at
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Mayr
authors.forename: Olaf
authors.initials: O
authors.lastname: Merkel
authors.forename: Sepp D
authors.initials: SD
authors.lastname: Kohlwein
authors.forename: Boris R
authors.initials: BR
authors.lastname: Gebhardt
authors.forename: Hansjosef
authors.initials: H
authors.lastname: Böhles
authors.forename: Ulrike
authors.initials: U
authors.lastname: Fötschl
authors.forename: Johannes
authors.initials: J
authors.lastname: Koch
authors.forename: Michaela
authors.initials: M
authors.lastname: Jaksch
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
authors.forename: Rita
authors.initials: R
authors.lastname: Horváth
authors.forename: Peter
authors.initials: P
authors.lastname: Freisinger
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sperl
mesh_terms: D000140:Acidosis, Lactic / Q000150:complications / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D002312:Cardiomyopathy, Hypertrophic / Q000150:complications / Q000378:metabolism; D002478:Cells, Cultured; D004734:Energy Metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005816:Genetic Complementation Test; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D008931:Mitochondria, Muscle / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000172:deficiency* / Q000235:genetics; D008969:Molecular Sequence Data; D009123:Muscle Hypotonia / Q000150:complications / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D010085:Oxidative Phosphorylation; D010375:Pedigree; D028061:Phosphate Transport Proteins / Q000172:deficiency* / Q000235:genetics; D010710:Phosphates / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D035781:Siblings
chemical_list: D024101:Mitochondrial Proteins; D028061:Phosphate Transport Proteins; D010710:Phosphates; C422067:SLC25A3 protein, human; D000255:Adenosine Triphosphate