Home LiteratureArticle Details
PMID: 19001123 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Cardiolipin provides an essential activating platform for caspase-8 on mitochondria.

The Journal of cell biology ·Vol. 183 ·No. 4 ·2008-11-17 ·Pages 681-96

Gonzalvez F, Schug ZT, Houtkooper RH, MacKenzie ED, Brooks DG, Wanders RJ, Petit PX, Vaz FM, Gottlieb E

Abstract

Cardiolipin is a mitochondria-specific phospholipid known to be intimately involved with apoptosis. However, the lack of appropriate cellular models to date restricted analysis of its role in cell death. The maturation of cardiolipin requires the transacylase tafazzin, which is mutated in the human disorder Barth syndrome. Using Barth syndrome patient-derived cells and HeLa cells in which tafazzin was knocked down, we show that cardiolipin is required for apoptosis in the type II mitochondria-dependent response to Fas stimulation. Cardiolipin provides an anchor and activating platform for caspase-8 translocation to, and embedding in, the mitochondrial membrane, where it oligomerizes and is further activated, steps that are necessary for an efficient type II apoptotic response.

MeSH Terms
Acyltransferases Apoptosis/physiology Cardiolipins/genetics,metabolism Caspase 8/genetics,metabolism HeLa Cells Humans Mitochondria/enzymology,metabolism Mitochondrial Membranes/enzymology Mitochondrial Proteins/genetics,metabolism Protein Transport/physiology Transcription Factors/genetics,metabolism fas Receptor/genetics,metabolism
Chemicals
Cardiolipins FAS protein, human Mitochondrial Proteins Transcription Factors fas Receptor Acyltransferases TAFAZZIN protein, human CASP8 protein, human Caspase 8
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Gonzalvez Francois
Cancer Research UK, The Beatson Institute for Cancer Research, Glasgow, Scotland, UK.
Schug Zachary T
Houtkooper Riekelt H
MacKenzie Elaine D
Brooks David G
Wanders Ronald J A
Petit Patrice X
Vaz Frédéric M
Gottlieb Eyal
References (52)
52 references, click to expand
  1. Role of cardiolipin on tBid and tBid/Bax synergistic effects on yeast mitochondria.
    Cell Death Differ. 2005 Jun;12(6):659-67 PMID: 15818414
  2. Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor.
    EMBO J. 1995 Nov 15;14(22):5579-88 PMID: 8521815
  3. The expanding role of mitochondria in apoptosis.
    Genes Dev. 2001 Nov 15;15(22):2922-33 PMID: 11711427
  4. An X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leucocytes.
    J Neurol Sci. 1983 Dec;62(1-3):327-55 PMID: 6142097
  5. The interaction between tBid and cardiolipin or monolysocardiolipin.
    Biochem Biophys Res Commun. 2005 May 13;330(3):865-70 PMID: 15809076
  6. An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9.
    J Biol Chem. 1999 Apr 23;274(17):11549-56 PMID: 10206961
  7. The enzymatic function of tafazzin.
    J Biol Chem. 2006 Dec 22;281(51):39217-24 PMID: 17082194
  8. Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane.
    Cell. 2002 Nov 1;111(3):331-42 PMID: 12419244
  9. Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally.
    Immunity. 1998 Aug;9(2):267-76 PMID: 9729047
  10. Mitochondrial membrane contact sites of yeast. Characterization of lipid components and possible involvement in intramitochondrial translocation of phospholipids.
    J Biol Chem. 1991 Jun 5;266(16):10047-9 PMID: 2037561
  11. Mitochondrial contact sites. Lipid composition and dynamics.
    J Biol Chem. 1990 Nov 5;265(31):18797-802 PMID: 2172233
  12. BAR: An apoptosis regulator at the intersection of caspases and Bcl-2 family proteins.
    Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2597-602 PMID: 10716992
  13. Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors.
    Nat Chem Biol. 2005 Sep;1(4):223-32 PMID: 16408039
  14. Microarray reveals differences in both tumors and vascular specific gene expression in de novo CD5+ and CD5- diffuse large B-cell lymphomas.
    Cancer Res. 2003 Jan 1;63(1):60-6 PMID: 12517778
  15. In situ trapping of activated initiator caspases reveals a role for caspase-2 in heat shock-induced apoptosis.
    Nat Cell Biol. 2006 Jan;8(1):72-7 PMID: 16362053
  16. X-linked dilated cardiomyopathy with neutropenia, growth retardation, and 3-methylglutaconic aciduria.
    J Pediatr. 1991 Nov;119(5):738-47 PMID: 1719174
  17. FLASH links the CD95 signaling pathway to the cell nucleus and nuclear bodies.
    EMBO J. 2007 Jan 24;26(2):391-401 PMID: 17245429
  18. Improved methods to isolate and subfractionate rat liver mitochondria. Lipid composition of the inner and outer membrane.
    Biochim Biophys Acta. 1990 Jan 29;1021(2):217-26 PMID: 2154259
  19. Association of active caspase 8 with the mitochondrial membrane during apoptosis: potential roles in cleaving BAP31 and caspase 3 and mediating mitochondrion-endoplasmic reticulum cross talk in etoposide-induced cell death.
    Mol Cell Biol. 2004 Aug;24(15):6592-607 PMID: 15254227
  20. Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors.
    Cell. 1998 Aug 21;94(4):481-90 PMID: 9727491
  21. Insights into the regulatory mechanism for caspase-8 activation.
    Mol Cell. 2003 Feb;11(2):543-9 PMID: 12620240
  22. Neonatal, lethal noncompaction of the left ventricular myocardium is allelic with Barth syndrome.
    Am J Hum Genet. 1997 Oct;61(4):868-72 PMID: 9382097
  23. Cardiolipin deficiency in X-linked cardioskeletal myopathy and neutropenia (Barth syndrome, MIM 302060): a study in cultured skin fibroblasts.
    J Pediatr. 2002 Nov;141(5):729-33 PMID: 12410207
  24. tBid interaction with cardiolipin primarily orchestrates mitochondrial dysfunctions and subsequently activates Bax and Bak.
    Cell Death Differ. 2005 Jun;12(6):614-26 PMID: 15818416
  25. Turnover of fatty acids in rat liver cardiolipin: comparison with other mitochondrial phospholipids.
    Lipids. 1976 Jan;11(1):61-6 PMID: 1250068
  26. Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner.
    J Cell Biol. 1999 Jan 25;144(2):281-92 PMID: 9922454
  27. Differential gene expression patterns in HER2/neu-positive and -negative breast cancer cell lines and tissues.
    Am J Pathol. 2002 Oct;161(4):1171-85 PMID: 12368191
  28. Cardiolipin provides specificity for targeting of tBid to mitochondria.
    Nat Cell Biol. 2000 Oct;2(10):754-61 PMID: 11025668
  29. The role of mitochondrial factors in apoptosis: a Russian roulette with more than one bullet.
    Cell Death Differ. 2002 Oct;9(10):1031-42 PMID: 12232790
  30. Monolysocardiolipins accumulate in Barth syndrome but do not lead to enhanced apoptosis.
    J Lipid Res. 2005 Jun;46(6):1182-95 PMID: 15805542
  31. Defective remodeling of cardiolipin and phosphatidylglycerol in Barth syndrome.
    Biochem Biophys Res Commun. 2000 Dec 20;279(2):378-82 PMID: 11118295
  32. Inactivation of caspase-8 on mitochondria of Bcl-xL-expressing MCF7-Fas cells: role for the bifunctional apoptosis regulator protein.
    J Biol Chem. 2002 Feb 8;277(6):4351-60 PMID: 11733517
  33. Potentiation of neuroblastoma metastasis by loss of caspase-8.
    Nature. 2006 Jan 5;439(7072):95-9 PMID: 16397500
  34. A novel X-linked gene, G4.5. is responsible for Barth syndrome.
    Nat Genet. 1996 Apr;12(4):385-9 PMID: 8630491
  35. The cardiolipin-binding domain of Bid affects mitochondrial respiration and enhances cytochrome c release.
    Apoptosis. 2004 Sep;9(5):533-41 PMID: 15314281
  36. Two CD95 (APO-1/Fas) signaling pathways.
    EMBO J. 1998 Mar 16;17(6):1675-87 PMID: 9501089
  37. Up-regulation of Bcl-xL expression protects CD40-activated human B cells from Fas-mediated apoptosis.
    Cell Immunol. 1996 Oct 10;173(1):149-54 PMID: 8871610
  38. Identification of the cytolinker plectin as a major early in vivo substrate for caspase 8 during CD95- and tumor necrosis factor receptor-mediated apoptosis.
    Mol Cell Biol. 2000 Aug;20(15):5665-79 PMID: 10891503
  39. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta.
    Mol Cell. 2002 Aug;10(2):417-26 PMID: 12191486
  40. Interdimer processing mechanism of procaspase-8 activation.
    EMBO J. 2003 Aug 15;22(16):4132-42 PMID: 12912912
  41. Cardiolipin deficiency releases cytochrome c from the inner mitochondrial membrane and accelerates stimuli-elicited apoptosis.
    Cell Death Differ. 2007 Mar;14(3):597-606 PMID: 16888643
  42. Cardiolipin metabolism and Barth Syndrome.
    Prog Lipid Res. 2006 Mar;45(2):91-101 PMID: 16442164
  43. The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress.
    Science. 2004 May 7;304(5672):843-6 PMID: 15073321
  44. Cardiolipin: setting the beat of apoptosis.
    Apoptosis. 2007 May;12(5):877-85 PMID: 17294083
  45. Proapoptotic Bid binds to monolysocardiolipin, a new molecular connection between mitochondrial membranes and cell death.
    Cell Death Differ. 2003 Dec;10(12):1300-9 PMID: 12894218
  46. Cytochrome c release from mitochondria proceeds by a two-step process.
    Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1259-63 PMID: 11818574
  47. The pro-apoptotic Bcl-2 family member tBid localizes to mitochondrial contact sites.
    BMC Cell Biol. 2001;2:22 PMID: 11716782
  48. Let-7 expression defines two differentiation stages of cancer.
    Proc Natl Acad Sci U S A. 2007 Jul 3;104(27):11400-5 PMID: 17600087
  49. Activation of initiator caspases through a stable dimeric intermediate.
    J Biol Chem. 2002 Dec 27;277(52):50761-7 PMID: 12399450
  50. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis.
    Cell. 1998 Aug 21;94(4):491-501 PMID: 9727492
  51. Loss of molecular interaction between cytochrome c and cardiolipin due to lipid peroxidation.
    Biochem Biophys Res Commun. 1999 Oct 22;264(2):343-7 PMID: 10529366
  52. Bid-cardiolipin interaction at mitochondrial contact site contributes to mitochondrial cristae reorganization and cytochrome C release.
    Mol Biol Cell. 2004 Jul;15(7):3061-72 PMID: 15107464
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.200803129
Published
2008-11-17
Epub
2008-00-10
Pages
681-96
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2582890
Subset
IM
Grants
NICHD NIH HHS · HD-2406 · United States
Cancer Research UK · United Kingdom
Corrections
CommentIn
PMID: 19001131
External Links
PubMed source DOI: 10.1083/jcb.200803129 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2