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
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / biosynthesis
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BH3 Interacting Domain Death Agonist Protein
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Cardiolipins / metabolism*
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Carrier Proteins / pharmacology
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Cell Respiration
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Cytochromes c / metabolism
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Energy Metabolism
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Membrane Proteins / deficiency
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Membrane Proteins / genetics
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Mitochondria / drug effects
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Mitochondria / genetics
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Mitochondria / metabolism*
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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Saccharomyces cerevisiae / cytology*
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Saccharomyces cerevisiae / drug effects
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism*
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Transferases (Other Substituted Phosphate Groups) / deficiency
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Transferases (Other Substituted Phosphate Groups) / genetics
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bcl-2-Associated X Protein
Substances
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BH3 Interacting Domain Death Agonist Protein
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Cardiolipins
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Carrier Proteins
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Membrane Proteins
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Proto-Oncogene Proteins c-bcl-2
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bcl-2-Associated X Protein
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Adenosine Triphosphate
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Cytochromes c
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Transferases (Other Substituted Phosphate Groups)
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cardiolipin synthetase