Recombinant human mitochondrial transcription factor A stimulates mitochondrial biogenesis and ATP synthesis, improves motor function after MPTP, reduces oxidative stress and increases survival after endotoxin

Mitochondrion. 2011 Jan;11(1):108-18. doi: 10.1016/j.mito.2010.08.004. Epub 2010 Aug 18.

Abstract

Recombinant human mitochondrial transcription factor A protein (rhTFAM) was evaluated for its acute effects on cultured cells and chronic effects in mice. Fibroblasts incubated with rhTFAM acutely increased respiration in a chloramphenicol-sensitive manner. SH-SY5Y cells showed rhTFAM concentration-dependent reduction of methylpyridinium (MPP(+))-induced oxidative stress and increases in lowered ATP levels and viability. Mice treated with weekly i.v. rhTFAM showed increased mitochondrial gene copy number, complex I protein levels and ATP production rates; oxidative damage to proteins was decreased ~50%. rhTFAM treatment improved motor recovery rate after treatment with MPTP and dose-dependently improved survival in the lipopolysaccharide model of endotoxin sepsis.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / administration & dosage
  • Adenosine Triphosphate / biosynthesis*
  • Animals
  • Cell Line, Tumor
  • Cell Respiration / drug effects
  • Cell Survival
  • DNA, Mitochondrial / drug effects
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism
  • DNA-Binding Proteins / administration & dosage
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / pharmacology*
  • Endotoxemia / drug therapy
  • Endotoxemia / mortality*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / physiology
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / administration & dosage
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Mitochondrial Proteins / pharmacology*
  • Motor Activity / drug effects
  • Motor Activity / physiology*
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / physiology
  • Oxidative Stress / drug effects*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology*
  • Transcription Factors / administration & dosage
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Factors / pharmacology*

Substances

  • DNA, Mitochondrial
  • DNA-Binding Proteins
  • Mitochondrial Proteins
  • Recombinant Proteins
  • Transcription Factors
  • mitochondrial transcription factor A
  • Adenosine Triphosphate
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine