Skip to main content
Log in

The roles of Bid

  • Published:
Apoptosis Aims and scope Submit manuscript

Abstract

Bid is an abundant pro-apoptotic protein of the Bcl-2 family that is crucial for death receptor-mediated apoptosis in many cell systems. Bid action has been proposed to involve the mitochondrial re-location of its truncated form, tBid, to facilitate the release of apoptogenic proteins like cytochrome c. However, the precise mechanism of (t)Bid action is unknown. To advance our knowledge, this review evaluates the basic steps of Bid activation—caspase cleavage, dissociation of tBid, and lipid-mediated mitochondrial relocation—and their structure-function aspects. Relevant current information is thoroughly examined to outline the problems that hamper our understanding of the possible roles of Bid in cell life and death, and suggest valuable directions for obtaining a clarification of its pro-apoptotic mechanism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Adams JM, Cory S Bcl-2 proteins, arbiters of cell survival. Science 1998; 281: 1322–1326.

    Google Scholar 

  2. Korsmeyer SJ, Wei MC, Saito M, et al Pro-apoptotic cascade activates BID, which oligomerizes Bak or Bax into pores that result in the release of cytochrome c. Cell Death Diff 2000; 7: 1166–1173.

    Google Scholar 

  3. Martinou J-C, Green DR Breaking the mitochondrial barrier. Nature Reviews Mol Cell Biol 2001; 2: 63–67.

    Google Scholar 

  4. Wang K, Yin XM, Chao DT, Milliman CL, Korsmeyer SJ BID: A novel BH3 domain-only death agonist. Genes Develop 1996; 10: 2859–2869.

    Google Scholar 

  5. Cheng EH, Wei MC, Weiler S, Flavell RA, Mak TW, Lindsten T, Korsmeyer SJ BCL-2, BCL-X(L) sequester BH3 domainonly molecules preventing BAX-and BAK-mediated mitochondrial apoptosis. Mol Cell 2001; 8: 705–711.

    Google Scholar 

  6. Luo X, Budihardjo I, Zou H, Slaughter C, Wang X Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell death receptors. Cell 1998; 94: 481–490.

    Google Scholar 

  7. Li H, Zhu H, Xu C, Yuan J Cleavage of BID by Caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 1998; 94: 491–501.

    Google Scholar 

  8. Gross A, Yin XM, Wang K, et al Caspase cleaved BID targets mitochondria and is required for cytochrome c release while BCL-XL prevents this release but not tumor necrosis factor death. J Biol Chem 1999; 274: 1156–1163.

    Google Scholar 

  9. Kim TH, Zhao Y, Barber MJ, Kuharsky DK, Yin XM Bidinduced cytochrome c release is mediated by a pathway independent of mitochondrial permeability transition pore and Bax. J Biol Chem 2000; 275: 39474–39481.

    Google Scholar 

  10. Yamada H, Tada-Oikawa ST, Uchida A, Kawanishi S TRAIL causes cleavage of Bid by caspase-8 and loss of mitochondrial membrane potential resulting in apoptosis in BJAB cells. Biochem Biophys Res Commun 1999; 265: 130–133.

    Google Scholar 

  11. Deng Y, Lin Y, Wu X TRIAL-induced apoptosis requires Baxdependent mitochondrial release of Smac/DIABLO. Genes Dev 2002; 16: 33–45.

    Google Scholar 

  12. Yin XM, Wang K, Gross A, et al Bid-deficient mice are resistant to Fas-induced hepatocellular apoptosis. Nature 1999; 400: 886–891.

    Google Scholar 

  13. Wei MC, Lindsen T, Mootha VK, et al tBID, a membranetargeted death ligand, oligomerizes BAK to release cytochrome c. Genes Dev 2000; 14: 2060–2071.

    Google Scholar 

  14. Wei MC, Zong WX, Cheng EH, et al Proapoptotic BAX and BAK: A requisite gateway to mitochondrial dysfunction and death. Science 2001; 292: 62462–62466.

    Google Scholar 

  15. Eskes R, Desangher S, Antonsson B, Martinou J-C Bid induces oligomerization and insertion of Bax into the outer mitochondrial membrane. Mol Cell Biol 2000; 20: 929–935.

    Google Scholar 

  16. Scorrano L, Ashiya M, Buttle K, Weiler S, Oakes SA, Mannella CA, Korsmeyer SJ A distinct pathway remodels mitochondrial cristae and mobilizes cytochrome c during apoptosis. Dev Cell 2002; 2: 55–67.

    Google Scholar 

  17. Kudla G, Montessuit S, Eskes R, Berrier C, Martinou J-C, Ghazi A, Antonsson B The destabilisation of lipid membranes induced by the C-terminal fragment of caspase 8-cleaved Bid is inhibited by the N-terminal fragment. J Biol Chem 2000; 275: 22713–22718.

    Google Scholar 

  18. Zha J, Weiler S, Oh K, Wei MC, Korsmeyer SJ Posttranslational N-myristoylation of BID as a molecular switch for targeting to mitochondria and apoptosis. Science 2000; 290: 1761–1765.

    Google Scholar 

  19. Grinberg M, Sarig R, Zaltsman Y, Frumkin D, Grammatikakis N, Reuveny E, Gross A tBID homooligomerizes in the mitochondrial membrane to induce apoptosis. J Biol Chem 2002; 277: 12237–12245.

    Google Scholar 

  20. Madesh M, Antonsson B, Srinivasula SM, Alnemri ES, Hajnoczky G Rapid kinetics of tBid-induced cytochrome c and Smac/DIABLO release and mitochondrial depolarization. J Biol Chem 2002; 277: 5651–5659.

    Google Scholar 

  21. Kluck R, Degli Esposti M, Perkins G, et al The pro-apoptotic proteins, Bid and Bax, cause a limited permeabilization of the mitochondrial outer membrane that is enhanced by cytosol. J Cell Biol 1999; 147: 809–822.

    Google Scholar 

  22. Lutter M, Fang M, Luo X, Nishijima M, Xie X, Wang X Cardiolipin provides specificity for targeting of tBid to mitochondria. Nature Cell Biol 2000; 2: 754–756.

    Google Scholar 

  23. Zhai D, Miao Q, Xin X, Yang F Leakage and aggregation of phospholipid vesicles induced by the BH3-only Bcl-2-family member, BID. Eur J Biochem 2001; 268: 48–55.

    Google Scholar 

  24. Degli Esposti M, Erler JT, Hickman JH, Dive C Bid, a widely expressed pro-apoptotic protein of the Bcl-2 family, displays lipid transfer activity. Mol Cell Biol 2001; 21: 7268–7276.

    Google Scholar 

  25. Degli Esposti M Sequence and functional similarities between pro-apoptotic Bid and plant lipid transfer proteins. Biochim Biophys Acta 2002; 1553: 331–340.

    Google Scholar 

  26. Chou JJ, Li H, Salvesen GS, Yuan J, Wagner G Solution structure of BID, an intracellular amplifier of apoptotic signaling. Cell 1999; 96: 615–624.

    Google Scholar 

  27. McDonnell JM, Fushman D, Milliman C, Korsmeyer SJ, Cowburn D Solution structure of the proapoptotic molecule BID: A structural basis for apoptotic agonists and antagonists. Cell 1999; 96: 625–634.

    Google Scholar 

  28. Suzuki M, Youle RJ, Tjandra N Structure of Bax: Coregulation of dimer formation and intracellular location. Cell 2000; 103: 645–654.

    Google Scholar 

  29. Losonczi JA, Olejniczak ET, Betz SF, Harlan JE, Mack J, Fesik SW NMR studies of the anti-apoptotic protein Bcl-xL in micelles. Biochemistry 2000; 39: 11024–11033.

    Google Scholar 

  30. Liu D, Huang Z Synthetic peptides and non-peptidic molecules as probes of structure and function of Bcl-2 family proteins and modulators of apoptosis. Apoptosis 2001; 6: 453–462.

    Google Scholar 

  31. Desagher S, Osen-Sand A, Nichols A, et al Bid-induced conformational change of Bax is responsible for mitochondrial cytochrome c release during apoptosis. J Cell Biol 1999; 144: 891–901.

    Google Scholar 

  32. Hsu YT, Youle RJ Nonionic detergents induces dimerization among members of the Bcl-2 family. J Biol Chem 1997; 272: 13829–13834.

    Google Scholar 

  33. Antonsson B, Montessuit S, Lauper S, Eskes R, Martinou J-C Bax oligomerization is required for channel-forming activity in liposomes and to trigger cytochrome c release from mitochondria. Biochem J 2000; 345: 271–278.

    Google Scholar 

  34. Tan Y, Ting AE Non-ionic detergent affects the conformation of a functionally active mutant of bcl-XL. Prot Engin 2000; 13: 887–892.

    Google Scholar 

  35. Bhakdi S, Fussle R, Tranum-Jensen J Staphylococcal alphatoxin: Oligomerization of hydrophilic monomers to form amphiphilic hexamers induced through contact with deoxycholate detergent micelles. Proc Natl Acad Sci USA 1981; 78: 5475–5479.

    Google Scholar 

  36. Vander Goot F, Pattus F, Wong KR, Buckley JT Oligomerization of the channel-forming toxin aerolysin precedes insertion into lipid bilayers. Biochemistry 1993; 32: 2636–2642.

    Google Scholar 

  37. Footz TK, Birren B, Minoshima S, et al The gene for death agonist Bid maps to the region of human 22q11.2 duplicated in cat eye syndrome chromosomes and mouse chromosome 6. Genomics 1998; 51: 472–475.

    Google Scholar 

  38. Krajewska M, Mai JK, Zapata JM, Ashwell KW, Schendel SL, Reed JC, Krajewski S Dynamics of expression of apoptosisregulatory proteins Bid, Bcl-2, Bcl-X, Bax and Bak during development of murine nervous system. Cell Death Differ 2002; 9: 145–157.

    Google Scholar 

  39. Tafani M, Karpinich NO, Hurster KA, Pastorino JG, Schneider T, Russo MA, Farber JL Cytochrome c release upon Fas receptor activation depends on translocation of full-length bid and the induction of the mitochondrial permeability transition. J Biol Chem 2002; 277: 10073–10082.

    Google Scholar 

  40. Tremblay JM, Helmkamp GM, Yarbrough LR Limited proteolysis of rat phosphatidylinositol transfer protein by trypsin cleaves the C terminus, enhances binding to lipid vesicles, and reduces phospholipid transfer activity. J Biol Chem 1996; 271: 21075–21080.

    Google Scholar 

  41. Nechtustan A, Smith CL, Lamensdorf I, Yoon S, Youle RJ Bax and Bak coalesce into novel mitochondria-associated clusters during apoptosis. J Cell Biol 2001; 153: 1265–1276.

    Google Scholar 

  42. Higuchi H, Miyoshi H, Bronk SF, Zhang H, Dean N, Gores GJ Bid antisense attenuates bile acid-induced apoptosis and cholestatic liver injury. J Pharmacol Exp Ther 2001; 299: 866–873.

    Google Scholar 

  43. Lutter M, Perkins GA, Wang X The pro-apoptotic Bcl-2 family member tBid localizes to mitochondrial contact sites. BMC Cell Biol 2002; 2: 22.

    Google Scholar 

  44. Bossy-Wetzel E, Green DR Caspases induce cytochrome c release from mitochondria by activating cytosolic factors. J Biol Chem 1999; 274: 17484–17490.

    Google Scholar 

  45. Barry M, Heibein JA, Pinkowski MJ, Lee SF, Moyer RW, Green DR, Bleackley RC, Granzyme B short-circuits the need for caspase 8 activity during granule-mediated cytotoxic T-lymphocyte killing by directly cleaving Bid. Mol Cell Biol 2000; 20: 3781–3794.

    Google Scholar 

  46. Alimonti JB, Shi L, Baijal PK, Greenberg AH Granzyme B induces BID-mediated cytochrome c release and mitochondrial permeability transition. J Biol Chem 2001; 276: 6974–6982.

    Google Scholar 

  47. Stoka V, Turk B, Schendel SL, et al Lysosomal protease pathways to apoptosis. Cleavage of Bid, not procaspases, is the most likely route. J Biol Chem 2001; 276: 3149–3157.

    Google Scholar 

  48. Chen M, He H, Zhan S, Krajewski S, Reed JC, Gottlieb RA Bid is cleaved by calpain to an active fragment in vitro and during myocardial ischemia/reperfusion. J Biol Chem 2001; 276: 30724–30728.

    Google Scholar 

  49. Desagher S, Osen-Sand A, Montessuit S, et al Phosphorylation of Bid by casein kinases I and II regulates its cleavage by caspase 8. Mol Cell 2001; 8: 601–611.

    Google Scholar 

  50. Schendel SL, Azimov R, Pawlowski K, Godzik A, Kagan BL, Reed JC Ion channel activity of the BH3 only Bcl-2 family member, BID. J Biol Chem 1999; 274: 21932–21936.

    Google Scholar 

  51. Wang X The expanding role of mitochondria in apoptosis. Genes Dev 2001; 15: 2922–2933.

    Google Scholar 

  52. Degli Esposti M Lipids, cardiolipin and apoptosis: A greasy licence to kill. Cell Death Diff 2002; 9: 234–236.

    Google Scholar 

  53. Alonso A, Goni FM, Buckley JT Lipids favoring inverted phase enhance the ability of aerolysin to permeabilize liposome bilayers. Biochemistry 2000; 39: 14019–14024.

    Google Scholar 

  54. Gomar J, Petit MC, Sodano P, et al Solution structure and lipid binding of a non-specific lipid transfer protein extracted from maize seeds. Protein Sci 1996; 5: 565–577.

    Google Scholar 

  55. Douliez JP, Michon T, Marion D Steady-state tyrosine fluorescence to study the lipid-binding properties of a wheat nonspecific lipid-transfer protein (nsLTP1). Biochim Biophys Acta 2000; 1467: 65–72.

    Google Scholar 

  56. Tassin S, Broekaert WF, Marion D, et al Solution structure of Ace-AMP1, a potent antimicrobial protein extracted from onion seeds. Structural analogies with plant nonspecific lipid transfer proteins. Biochemistry 1998; 37: 3623–3637.

    Google Scholar 

  57. Shaughnessy S, Smith ER, Storch J, Fried SK Adipocyte metabolism in adipocyre fatty acid binding protein knockout (aP2-/-) mice after short-term high-fat feeding. Functional compensation by the keratinocyte fatty acid binding protein. Diabetes 2000; 49: 904–911.

    Google Scholar 

  58. Cifone MG, Roncaioli P, De Maria R, Camarda G, Santoni A, Ruberti G, Testi R Multiple pathways originate at the Fas/APO-1 (CD95) receptor: Sequential involvement of phosphatidylcholine-specific phospholipase C and acidic sphingomyelinase in the proagation of the apoptotic signal. EMBO J 1995; 14: 5859–5868.

    Google Scholar 

  59. Atsumi G, Tajima M, Hadano A, Nakatani Y, Murakami M, Kudo I Fas-induced arachidonic acid release is mediated by Ca2+-independent phospholipase A2 but not cytosolic phospholipase A2, which undergoes proteolytic inactivation. J Biol Chem 1998; 273: 13870–13877.

    Google Scholar 

  60. Scorrano L, Penzo D, Petronilli V, Pagano F, Bernardi P Arachidonic acid causes cell death through the mitochondrial permeability transition. J Biol Chem 2001; 276: 12035–12040.

    Google Scholar 

  61. Williams SD, Gottlieb RA Inhibition of mitochondrial calcium-independent phospholipase A2 (iPLA2) attenuates mitochondrial phospholipid loss and is cardioprotective. Biochem J 2002; 352: 23–32.

    Google Scholar 

  62. Van Loo G, Demol H, van Gurp M, et al A matrix-assisted laser desorption ionization post-source decay (MALDI-PSD) analysis of proteins released from isolated liver mitochondria treated with recombinant truncated Bid. Cell Death Differ 2002; 9: 301–308.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Esposti, M.D. The roles of Bid. Apoptosis 7, 433–440 (2002). https://doi.org/10.1023/A:1020035124855

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1020035124855

Navigation