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.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- CL:
-
cardiolipin
- PC:
-
phosphatidylcholine
- PE:
-
phosphatidylethanolamine
- PG:
-
phosphatidylglycerol
- PI:
-
phosphatidylinositol
- PS:
-
phosphatidylserine
- DiOC6(3):
-
3,3′-dihexyloxacarbocyanine iodide
- ΔΨm:
-
mitochondrial membrane potential
- FCCP:
-
fluorocarbonyl cyanide m-chlorophenylhydrazone
- NAO:
-
nonylacridine orange
- TPP+:
-
tetraphenylphosphonium
References
Hoch FL (1998) Cardiolipins and mitochondrial proton-selective leakage. J. Bioenerg. Biomembr. 30: 511–532
Schlame M, Rua D and Greenberg ML (2000) The biosynthesis and functional role of cardiolipin. Prog. Lipid Res. 39: 257–288
Dale MP and Robinson NC (1988) Synthesis of cardiolipin derivatives with protection of the free hydroxyl: its application to the study of cardiolipin stimulation of cytochrome c oxidase. Biochemistry 27: 8270–8275
Robinson NC (1993) Functional binding of cardiolipin to cytochrome c oxidase. J. Bioenerg. Biomembr. 25: 153–163
Horvath LI, Drees M, Beyer K, Klingenberg M and Marsh D (1990) Lipid–protein interactions in ADP–ATP carrier/egg phosphatidylcholine recombinants studied by spin-label ESR spectroscopy. Biochemistry 29: 10664–10669
Jiang F, Ryan MT, Schlame M, Zhao M, Gu Z, Klingenberg M, Pfanner N and Greenberg ML (2000) Absence of cardiolipin in the crd1 null mutant results in decreased mitochondrial membrane potential and reduced mitochondrial function. J. Biol. Chem. 275: 22387–22394
Kagawa Y, Kandrach A and Racker E (1973) Partial resolution of the enzymes catalyzing oxidative phosphorylation. XXVI. Specificity of phospholipids required for energy transfer reactions. J. Biol. Chem. 248: 676–684
Serrano R, Kanner BI and Racker E (1976) Purification and properties of the proton-translocating adenosine triphosphatase complex of bovine heart mitochondria. J. Biol. Chem. 251: 2453–2461
Eble KS, Coleman WB, Hantgan RR and Cunningham CC (1990) Tightly associated cardiolipin in the bovine heart mitochondrial ATP synthase as analyzed by 31P nuclear magnetic resonance spectroscopy. J. Biol. Chem. 265: 19434–19440
Tuominen EK, Wallace CJ, Kinnunen PK, Zhu K, Clark-Lewis I, Craig DB and Rytomaa M (2002) Phospholipid–cytochrome c interaction: evidence for the extended lipid anchorage: ATP induces a conformational change in lipid-bound cytochrome c. J. Biol. Chem. 277: 8822–8882
Vayssière J-L, Petit PX, Risler Y and Mignotte B (1994) Commitment to apoptosis is associated with changes in mitochondrial biogenesis and activity in cell lines conditionally immortalized with simian virus 40. Proc. Natl. Acad. Sci. USA 91: 11752–11756
Petit PX, Lecoeur H, Zorn E, Dauguet C, Mignotte B and Gougeon ML (1995) Alterations of mitochondrial structure and function are early events of dexamethasone-induced thymocyte apoptosis. J. Cell Biol. 130: 157–167
Wang X (2001) The expanding role of mitochondria in apoptosis. Genes Dev. 15: 2922–2933
Newmeyer DD, Ferguson-Miller S, Kuwana T, Mackey MR, Perkins G, Ellisman MH, Latterich M, Schneiter R and Green DR (2003) Mitochondria: releasing power for life and unleashing the machineries of death Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. Cell 112: 481–490
Gross A, McDonnell JM and Korsmeyer SJ (1999) BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 13: 1899–1911
Martinou JC and Green DR (2001) Breaking the mitochondrial barrier. Nat. Rev. Mol. Cell Biol. 2: 63–67
Luo X, Budihardjo I, Zou H, Slaughter C and Wang X (1998) Bid, a bcl-2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface receptors. Cell 94: 481–490
Gross A, Yin XM, Wang K, Wei MC, Jockel J, Milliman C, Erdjument-Bromage H, Tempst P and Korsmeyer SJ (1999) Caspase cleaved BID targets mitochondria and is required for cytochrome c release, while BCL-XL prevents this release but not tumor necrosis factor-R1/Fas death. J. Biol. Chem. 274: 1156–1163
Barry M, Heibein JA, Pinkoski MJ, Lee SF, Moyer RW, Green DR and Bleackley RC (2000) Granzyme B short-circuits the need for caspase 8 activity during granule-mediated cytotoxic T-lymphocyte killing by directly cleaving Bid (in process citation). Mol. Cell. Biol. 20: 3781–3794
Stoka V, Turk B, Schendel SL, Kim TH, Cirman T, Snipas SJ, Ellerby LM, Bredesen D, Freeze H, Abrahamson M, Bromme D, Krajewski S, Reed JC, Yin XM, Turk V and Salvesen GS (2001) Lysosomal protease pathways to apoptosis. Cleavage of bid, not pro-caspases, is the most likely route. J. Biol. Chem. 276: 3149–3157
Chen M, He H, Zhan S, Krajewski S, Reed JC and Gottlieb RA (2001) Bid is cleaved by calpain to an active fragment in vitro and during myocardial ischemia/reperfusion. J. Biol. Chem. 276: 30724–30728
Li H, Zhu H, Xu CJ and Yuan J (1998) Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94: 491–501
Esposti MD (2002) The roles of Bid. Apoptosis 7: 433–440
Chou JJ, Li H, Salvesen GS, Yuan J and Wagner G (1999) Solution structure of BID, an intracellular amplifier of apoptotic signaling. Cell 96: 615–624
McDonnell JM, Fushman D, Milliman CL, Korsmeyer SJ and Cowburn D (1999) Solution structure of the proapoptotic molecule BID: a structural basis for apoptotic agonists and antagonists. Cell 96: 625–634
Esposti MD, Erler JT, Hickman JA and Dive C (2001) Bid, a widely expressed proapoptotic protein of the Bcl-2 family, displays lipid transfer activity. Mol. Cell. Biol. 21: 7268–7276
Hu X, Han Z, Wyche JH and Hendrickson EA (2003) Helix 6 of tBid is necessary but not sufficient for mitochondrial binding activity. Apoptosis 8: 277–289
Lutter M, Perkins GA and Wang X (2001) The pro-apoptotic Bcl-2 family member tBid localizes to mitochondrial contact sites. BMC Cell Biol. 2: 22
Esposti MD, Cristea IM, Gaskell SJ, Nakao Y, Dive C, Erler JT and Hickman JA (2003) Proapoptotic Bid binds to monolysocardiolipin, a new molecular connection between mitochondrial membranes and cell death. Cell Death Differ. 1: 1–10
Desagher S, Osen-Sand A, Nichols A, Eskes R, Montessuit S, Lauper S, Maundrell K, Antonsson B and Martinou JC (1999) Bid-induced conformational change of Bax is responsible for mitochondrial cytochrome c release during apoptosis. J. Cell Biol. 144: 891–901
Gonzalvez F, Pariselli F, Rameau C, Dupaigne P, Budihardjo I, Leducq N, Lutter M, Antonsson BSM, Martinou JC, Wang X, Diolez P, Bernard S and Petit PX (2005) t-Bid interaction with cardiolipin primarily orchestrate mitochondrial dysfunctions and subsequently activates Bax and Bak. Cell Death Differ. 40 (in press)
Ding WX, Ni HM, DiFrancesca D, Stolz DB and Yin XM (2004) Bid-dependent generation of oxygen radicals promotes death receptor activation-induced apoptosis in murine hepatocytes. Hepatology 40: 403–413
Scorrano L, Ashiya M, Buttle K, Weiler S, Oakes SA, Mannella CA and Korsmeyer SJ (2002) A distinct pathway remodels mitochondrial cristae and mobilizes cytochrome c during apoptosis. Dev. Cell 2: 55–67
Priault M, Cartron PF, Camougrand N, Antonsson B, Vallette FM and Manon S (2003) Investigation of the role of the C-terminus of Bax and of tc-Bid on Bax interaction with yeast mitochondria. Cell Death Differ. 10: 1068–1077
Pavlov EV, Priault M, Pietkiewicz D, Cheng EH, Antonsson B, Manon S, Korsmeyer SJ, Mannella CA and Kinnally KW (2001) A novel, high conductance channel of mitochondria linked to apoptosis in mammalian cells and Bax expression in yeast. J. Cell Biol. 155: 725–731
Iverson SL, Enoksson M, Gogvadze V, Ott M and Orrenius S (2004) Cardiolipin is not required for Bax-mediated cytochrome c release from yeast mitochondria. J. Biol. Chem. 279: 1100–1107
Priault M, Bessoule JJ, Grelaud-Coq A, Camougrand N and Manon S (2002) Bax-induced cell death in yeast depends on mitochondrial lipid oxidation. Eur. J. Biochem. 269: 5440–5450
Epand RF, Martinou JC, Fornallaz-Mulhauser M, Hughes DW and Epand RM (2002) The apoptotic protein tBid promotes leakage by altering membrane curvature. J. Biol. Chem. 277: 32632–32639
Priault M, Chaudhuri B, Clow A, Camougrand N and Manon S (1999) Investigation of bax-induced release of cytochrome c from yeast mitochondria permeability of mitochondrial membranes, role of VDAC and ATP requirement. Eur. J. Biochem. 260: 684–691
Priault M, Camougrand N, Chaudhuri B and Manon S (1999) Role of the C-terminal domain of Bax and Bcl-XL in their localization and function in yeast cells. FEBS Lett. 443: 225–228
Law RH, Manon S, Devenish RJ and Nagley P (1995) ATP synthase from Saccharomyces cerevisiae. Methods Enzymol. 260: 133–163
Kamo N, Muratsugu M, Hongoh M and Kobatake Y (1979) Membrane potential of mitochondria measured with an electrode to tetraphenylphosphonium and relationship between proton electrochemical gradient and phosphorylation potential in steady state. J. Membr. Biol. 49: 105–121
Leducq N, Delmas-Beauvieux MC, Bourdel-Marchasson I, Dufour S, Gallis JL, Canioni P and Diolez P (2000) Mitochondrial and energetic dysfunctions of the liver during normothermic reperfusion: protective effect of cyclosporine and role of the mitochondrial permeability transition pore. Transplant Proc. 32: 479–480
Rottenberg H (1984) Membrane potential and surface potential in mitochondria: uptake and binding of lipophilic cations. J. Membrane Biol. 81: 127–138
Okamoto K, Perlman PS and Butow RA (1998) The sorting of mitochondrial DNA and mitochondrial proteins in zygotes: preferential transmission of mitochondrial DNA to the medial bud. J. Cell Biol. 142: 613–623
Simbeni R, Pon L, Zinser E, Paltauf F and Daum G (1991) Mitochondrial membrane contact sites of yeast. Characterization of lipid components and possible involvement in intramitochondrial translocation of phospholipids. J. Biol. Chem. 266: 10047–10049
Pon L, Moll T, Vestweber D, Marshallsay B and Schatz G (1989) Protein import into mitochondria: ATP-dependent protein translocation activity in a submitochondrial fraction enriched in membrane contact sites and specific proteins. J. Cell Biol. 109: 2603–2616
Vitiello F and Zanetta JP (1978) Thin-layer chromatography of phospholipids. J. Chromatogr. 166: 637–640
Acknowledgements
This work was supported by grants from the Centre National de la Recherche Scientifique (CNRS), the ‘Association pour la Recherche contre le Cancer’ (ARC no. 4493 to PXP), the Conseil Régional d'Aquitaine and the Université de Bordeaux 2 (to SM). We also thank Professor JC Martinou for providing us with recombinant tBid (University of Geneva, Switzerland) and E Gottlieb (Beatson Institute for Cancer Research, Glasgow, UK) for a critical point of view.
Author information
Authors and Affiliations
Corresponding authors
Additional information
Edited by JC Martinou
Rights and permissions
About this article
Cite this article
Gonzalvez, F., Bessoule, JJ., Rocchiccioli, F. et al. Role of cardiolipin on tBid and tBid/Bax synergistic effects on yeast mitochondria. Cell Death Differ 12, 659–667 (2005). https://doi.org/10.1038/sj.cdd.4401585
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/sj.cdd.4401585
Keywords
This article is cited by
-
Lost in promiscuity? An evolutionary and biochemical evaluation of HSD10 function in cardiolipin metabolism
Cellular and Molecular Life Sciences (2022)
-
The molecular mechanism of a novel derivative of BTO-956 induced apoptosis in human myelomonocytic lymphoma cells
Apoptosis (2021)
-
Expressing and functional analysis of mammalian apoptotic regulators in yeast
Cell Death & Differentiation (2010)
-
New insights into apoptosis signaling by Apo2L/TRAIL
Oncogene (2010)
-
Giant unilamellar vesicles (GUVs) as a new tool for analysis of caspase-8/Bid-FL complex binding to cardiolipin and its functional activity
Cell Death & Disease (2010)
