Role of cardiolipin on tBid and tBid/Bax synergistic effects on yeast mitochondria.
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.
Gonzalvez
F
F
Institut Cochin, Team 'Cancer, Apoptosis and Mitochondria', CNRS UMR 8104/INSERM U567/Université ParisV, R. Descartes--24 rue du Faubourg Saint-Jacques, Paris, France.
Bessoule
J-J
JJ
Rocchiccioli
F
F
Manon
S
S
Petit
P X
PX
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D051023:BH3 Interacting Domain Death Agonist Protein; D002308:Cardiolipins / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D019069:Cell Respiration; D045304:Cytochromes c / Q000378:metabolism; D004734:Energy Metabolism; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017855:Transferases (Other Substituted Phosphate Groups) / Q000172:deficiency / Q000235:genetics; D051028:bcl-2-Associated X Protein
D051023:BH3 Interacting Domain Death Agonist Protein; D002308:Cardiolipins; D002352:Carrier Proteins; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D017855:Transferases (Other Substituted Phosphate Groups); C100091:cardiolipin synthetase