Mitochondrial Phosphate-Carrier Deficiency: A Novel Disorder of Oxidative Phosphorylation

Am J Hum Genet. 2007 Mar;80(3):478-84. doi: 10.1086/511788. Epub 2007 Jan 10.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis, Lactic / complications
  • Acidosis, Lactic / metabolism
  • Adenosine Triphosphate / metabolism
  • Alternative Splicing
  • Amino Acid Sequence
  • Cardiomyopathy, Hypertrophic / complications
  • Cardiomyopathy, Hypertrophic / 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*
  • Mitochondrial Proteins / genetics
  • Molecular Sequence Data
  • Muscle Hypotonia / complications
  • Muscle Hypotonia / metabolism
  • Mutation / genetics*
  • Oxidative Phosphorylation*
  • Pedigree
  • Phosphate Transport Proteins / deficiency*
  • Phosphate Transport Proteins / genetics
  • Phosphates / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism
  • Sequence Homology, Amino Acid
  • Siblings

Substances

  • Mitochondrial Proteins
  • Phosphate Transport Proteins
  • Phosphates
  • SLC25A3 protein, human
  • Adenosine Triphosphate

Associated data

  • RefSeq/NM_005888