Adenine nucleotide translocase is involved in a mitochondrial coupling defect in MFN2-related Charcot-Marie-Tooth type 2A disease

Neurogenetics. 2010 Feb;11(1):127-33. doi: 10.1007/s10048-009-0207-z. Epub 2009 Jul 18.

Abstract

Charcot-Marie-Tooth type 2A disease (CMT2A), a dominantly inherited peripheral neuropathy, is caused by mutations in MFN2, a mitochondrial fusion protein. Having previously demonstrated a mitochondrial coupling defect in CMT2A patients' fibroblasts, we here investigate mitochondrial oxygen consumption and the expression of adenine nucleotide translocase (ANT) and uncoupling proteins from eight other patients with the disease. The mitochondrial uncoupling was associated with a higher respiratory rate, essentially involving complex II proteins. Furthermore, a twofold increase in the expression of ANT led to the reduced efficiency of oxidative phosphorylation in CMT2A cells, suggesting that MFN2 plays a role in controlling ATP/ADP exchanges.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Charcot-Marie-Tooth Disease / enzymology*
  • Charcot-Marie-Tooth Disease / genetics*
  • Fibroblasts / metabolism
  • GTP Phosphohydrolases
  • Humans
  • Membrane Proteins / genetics*
  • Membrane Proteins / physiology
  • Mitochondria / metabolism*
  • Mitochondrial ADP, ATP Translocases / metabolism*
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / physiology
  • Models, Genetic
  • Mutation
  • Oxygen Consumption
  • Phosphorylation
  • Protein Isoforms
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Membrane Proteins
  • Mitochondrial Proteins
  • Protein Isoforms
  • Mitochondrial ADP, ATP Translocases
  • GTP Phosphohydrolases
  • MFN2 protein, human