Role of Cardiolipin on tBid and tBid/Bax Synergistic Effects on Yeast Mitochondria

Cell Death Differ. 2005 Jun;12(6):659-67. doi: 10.1038/sj.cdd.4401585.

Abstract

The apoptotic effector Bid regulates cell death at the level of mitochondria. Under its native state, Bid is a soluble cytosolic protein that undergoes proteolysis and yields a 15 kDa-activated form tBid (truncated Bid). tBid translocates to mitochondria and participates in cytochrome c efflux by a still unclear mechanism, some of them at least mediated by Bax. Using mitochondria isolated from wild-type and cardiolipin (CL)-synthase-less yeast strains, we observed that tBid perturbs mitochondrial bioenergetics by inhibiting state-3 respiration and ATP synthesis and that this effect was strictly dependent on the presence of CL. In a second set of experiments, heterologous coexpression of tBid and Bax in wild-type and CL-less yeast strains showed that (i) tBid binding and the subsequent alteration of mitochondrial bioenergetics increased Bax-induced cytochrome c release and (ii) the absence of CL favors Bax effects independently of the presence of t-Bid. These data support recent views suggesting a dual function of CL in mitochondria-dependent apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • BH3 Interacting Domain Death Agonist Protein
  • Cardiolipins / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Carrier Proteins / pharmacology
  • Cell Respiration
  • Cytochromes c / metabolism
  • Energy Metabolism
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Mitochondria / drug effects
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Transferases (Other Substituted Phosphate Groups) / deficiency
  • Transferases (Other Substituted Phosphate Groups) / genetics
  • bcl-2-Associated X Protein

Substances

  • BH3 Interacting Domain Death Agonist Protein
  • Cardiolipins
  • Carrier Proteins
  • Membrane Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Adenosine Triphosphate
  • Cytochromes c
  • Transferases (Other Substituted Phosphate Groups)
  • cardiolipin synthetase