BCL-2 improves oxidative phosphorylation and modulates adenine nucleotide translocation in mitochondria of cells harboring mutant mtDNA

J Biol Chem. 2003 Feb 21;278(8):5639-45. doi: 10.1074/jbc.M203080200. Epub 2002 Nov 12.

Abstract

Members of the BCL-2-related antiapoptotic family of proteins have been shown previously to regulate ATP/ADP exchange across the mitochondrial membranes and to prevent the loss of coupled mitochondrial respiration during apoptosis. We have found that BCL-2/BCL-x(L) can also improve mitochondrial oxidative phosphorylation in cells harboring pathogenic mutations in mitochondrial tRNA genes. The effect of BCL-2 overexpression in mutated cells was independent from apoptosis and was presumably associated with a modulation of adenine nucleotide exchange between mitochondria and cytosol. These results suggest that BCL-2 can regulate respiratory functions in response to mitochondrial distress by regulating the levels of adenine nucleotides.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenine Nucleotides / metabolism
  • Apoptosis / physiology*
  • Bone Neoplasms
  • Cytosol / metabolism
  • DNA, Mitochondrial / genetics*
  • Humans
  • Intracellular Membranes / enzymology
  • Mitochondria / metabolism*
  • Mitochondrial ADP, ATP Translocases / metabolism*
  • Osteosarcoma
  • Oxidative Phosphorylation*
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Tumor Cells, Cultured
  • bcl-X Protein

Substances

  • Adenine Nucleotides
  • BCL2L1 protein, human
  • DNA, Mitochondrial
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein
  • Mitochondrial ADP, ATP Translocases