Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

The many shapes of mitochondrial death

Oncogene volume 25, pages 4717–4724 (2006)Cite this article

Abstract

Mitochondria integrate apoptotic signalling by releasing cytochrome c and other proapoptotic cofactors needed for activation of effector caspases. Previously overlooked morphological changes, mitochondrial fragmentation and cristae remodelling, emerged as subroutines of the mitochondrial programme of apoptosis in mammalian cells, as well as in developmental cell death of Caenorhabditis elegans. Mitochondrial morphology results from fusion and fission processes, controlled by a growing set of ‘mitochondria-shaping’ proteins. Their levels and function appear to influence mitochondrial pathways of cell death, but mechanisms are largely unknown. An emerging model implicates different signals converging on mitochondria-shaping proteins to activate or deactivate them during apoptosis. In turn, these proteins can orchestrate changes in mitochondrial shape to insure cytochrome c release and progression of the apoptotic cascade. These therefore appear an appealing novel therapeutic target to modulate cell death in cancer.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  • Alexander C, Votruba M, Pesch UE, Thiselton DL, Mayer S, Moore A et al. (2000). Nat Genet 26: 211–215.

  • Amati-Bonneau P, Guichet A, Olichon A, Chevrollier A, Viala F, Miot S et al. (2005). Ann Neurol 58: 958–963.

  • Arnoult D, Grodet A, Lee YJ, Estaquier J, Blackstone C . (2005a). J Biol Chem 280: 35742–35750.

  • Arnoult D, Rismanchi N, Grodet A, Roberts RG, Seeburg DP, Estaquier J et al. (2005b). Curr Biol 15: 2112–2118.

  • Bach D, Pich S, Soriano FX, Vega N, Baumgartner B, Oriola J et al. (2003). J Biol Chem 278: 17190–17197.

  • Bassik MC, Scorrano L, Oakes SA, Pozzan T, Korsmeyer SJ . (2004). EMBO J 23: 1207–1216.

  • Breckenridge DG, Stojanovic M, Marcellus RC, Shore GC . (2003). J Cell Biol 160: 1115–1127.

  • Cereghetti GM, Stangherlin A, Scorrano L . (2006) Submitted.

  • Chami M, Prandini A, Campanella M, Pinton P, Szabadkai G, Reed JC et al. (2004). J Biol Chem 279: 54581–54589.

  • Chen H, Chomyn A, Chan DC . (2005). J Biol Chem 280: 26185–26192.

  • Chen H, Detmer SA, Ewald AJ, Griffin EE, Fraser SE, Chan DC . (2003). J Cell Biol 160: 189–200.

  • Chen KH, Guo X, Ma D, Guo Y, Li Q, Yang D et al. (2004). Nat Cell Biol 6: 872–883.

  • Chung JG, Yeh KT, Wu SL, Hsu NY, Chen GW, Yeh YW et al. (2001). Cancer Res 61: 8873–8879.

  • Cipolat S, de Brito OM, Dal Zilio B, Scorrano L . (2004). Proc Natl Acad Sci USA 101: 15927–15932.

  • Cipolat S, Rudka T, Hartmann D, Costa V, Serneels D, Craessaerts K et al. (2006) Submitted.

  • Claeys K, Verhoeven K, Zuchner S, Schroder JM, Vance JM, Timmerman V et al. (2005). J Peripher Nerv Syst 10: 16–17.

  • Danial NN, Korsmeyer SJ . (2004). Cell 116: 205–219.

  • De Vos KJ, Allan VJ, Grierson AJ, Sheetz MP . (2005). Curr Biol 15: 678–683.

  • Delettre C, Griffoin JM, Kaplan J, Dollfus H, Lorenz B, Faivre L et al. (2001). Hum Genet 109: 584–591.

  • Delettre C, Lenaers G, Griffoin JM, Gigarel N, Lorenzo C, Belenguer P et al. (2000). Nat Genet 26: 207–210.

  • Delettre C, Lenaers G, Pelloquin L, Belenguer P, Hamel CP . (2002). Mol Genet Metab 75: 97–107.

  • Fannjiang Y, Cheng WC, Lee SJ, Qi B, Pevsner J, McCaffery JM et al. (2004). Genes Dev 18: 2785–2797.

  • Ferre M, Amati-Bonneau P, Tourmen Y, Malthiery Y, Reynier P . (2005). Hum Mutat 25: 423–428.

  • Fong WG, Liston P, Rajcan-Separovic E, St Jean M, Craig C, Korneluk RG . (2000). Genomics 70: 113–122.

  • Foyouzi-Youssefi R, Arnaudeau S, Borner C, Kelley WL, Tschopp J, Lew DP et al. (2000). Proc Natl Acad Sci USA 97: 5723–5728.

  • Frank S, Gaume B, Bergmann-Leitner ES, Leitner WW, Robert EG, Catez F et al. (2001). Dev Cell 1: 515–525.

  • Frey TG, Mannella CA . (2000). Trends Biochem Sci 25: 319–324.

  • Frezza C, Cipolat S, de Brito OM, Micaroni M, Beznoussenko GV, Bartoli D et al. (2006) Submitted.

  • Germain M, Mathai JP, McBride HM, Shore GC . (2005). EMBO J 24: 1546–1556.

  • Griparic L, van der Wel NN, Orozco IJ, Peters PJ, van der Bliek AM . (2004). J Biol Chem 279: 18792–18798.

  • Harder Z, Zunino R, McBride H . (2004). Curr Biol 14: 340–345.

  • Ingerman E, Perkins EM, Marino M, Mears JA, McCaffery JM, Hinshaw JE et al. (2005). J Cell Biol 170: 1021–1027.

  • Ishihara N, Eura Y, Mihara K . (2004). J Cell Sci 117: 6535–6546.

  • Jagasia R, Grote P, Westermann B, Conradt B . (2005). Nature 433: 754–760.

  • James DI, Parone PA, Mattenberger Y, Martinou JC . (2003). J Biol Chem 278: 36373–36379.

  • Karbowski M, Arnoult D, Chen H, Chan DC, Smith CL, Youle RJ . (2004a). J Cell Biol 164: 493–499.

  • Karbowski M, Jeong SY, Youle RJ . (2004b). J Cell Biol 166: 1027–1039.

  • Karbowski M, Lee YJ, Gaume B, Jeong SY, Frank S, Nechushtan A et al. (2002). J Cell Biol 159: 931–938.

  • Koehler CM, Leuenberger D, Merchant S, Renold A, Junne T, Schatz G . (1999). Proc Natl Acad Sci USA 96: 2141–2146.

  • Koshiba T, Detmer SA, Kaiser JT, Chen H, McCaffery JM, Chan DC . (2004). Science 305: 858–862.

  • Labrousse AM, Zappaterra MD, Rube DA, van der Bliek AM . (1999). Mol Cell 4: 815–826.

  • Lam M, Dubyak G, Chen L, Nunez G, Miesfeld RL, Distelhorst CW . (1994). Proc Natl Acad Sci USA 91: 6569–6573.

  • Lee YJ, Jeong SY, Karbowski M, Smith CL, Youle RJ . (2004). Mol Biol Cell 15: 5001–5011.

  • Li C, Fox CJ, Master SR, Bindokas VP, Chodosh LA, Thompson CB . (2002). Proc Natl Acad Sci USA 99: 9830–9835.

  • Liston P, Fong WG, Korneluk RG . (2003). Oncogene 22: 8568–8580.

  • Liu JP, Sim AT, Robinson PJ . (1994). Science 265: 970–973.

  • Malka F, Guillery O, Cifuentes-Diaz C, Guillou E, Belenguer P, Lombes A et al. (2005). EMBO Rep 6: 853–859.

  • Marchbank NJ, Craig JE, Leek JP, Toohey M, Churchill AJ, Markham AF et al. (2002). J Med Genet 39: e47.

  • McNiven MA, Yoon Y, Pitts KR . (2000). Mol Biol Cell 11: 219A.

  • Meeusen S, McCaffery JM, Nunnari J . (2004). Science 305: 1747–1752.

  • Meeusen SL, Nunnari J . (2005). Curr Opin Cell Biol 17: 389–394.

  • Morris RL, Hollenbeck PJ . (1995). J Cell Biol 131: 1315–1326.

  • Mozdy AD, McCaffery JM, Shaw JM . (2000). J Cell Biol 151: 367–380.

  • Neuspiel M, Zunino R, Gangaraju S, Rippstein P, McBride HM . (2005). J Biol Chem 280: 25060–25070.

  • Nutt LK, Chandra J, Pataer A, Fang B, Roth JA, Swisher SG et al. (2002a). J Biol Chem 277: 20301–20308.

  • Nutt LK, Pataer A, Pahler J, Fang B, Roth J, McConkey DJ et al. (2002b). J Biol Chem 277: 9219–9225.

  • Olichon A, Baricault L, Gas N, Guillou E, Valette A, Belenguer P et al. (2003). J Biol Chem 278: 7743–7746.

  • Olichon A, Emorine LJ, Descoins E, Pelloquin L, Brichese L, Gas N et al. (2002). FEBS Lett 523: 171–176.

  • Orrenius S, Zhivotovsky B, Nicotera P . (2003). Nat Rev Mol Cell Biol 4: 552–565.

  • Pacher P, Hajnoczky G . (2001). EMBO J 20: 4107–4121.

  • Perfettini JL, Roumier T, Kroemer G . (2005). Trends Cell Biol 15: 179–183.

  • Pesch UE, Leo-Kottler B, Mayer S, Jurklies B, Kellner U, Apfelstedt-Sylla E et al. (2001). Hum Mol Genet 10: 1359–1368.

  • Pinton P, Ferrari D, Magalhaes P, Schulze-Osthoff K, Di VF, Pozzan T et al. (2000). J Cell Biol 148: 857–862.

  • Praefcke GJ, McMahon HT . (2004). Nat Rev Mol Cell Biol 5: 133–147.

  • Rizzuto R, Bernardi P, Pozzan T . (2000). J Physiol 529 (Part 1): 37–47, 37–47.

  • Satoh M, Hamamoto T, Seo N, Kagawa Y, Endo H . (2003). Biochem Biophys Res Commun 300: 482–493.

  • Scorrano L . (2003). Cell Death Differ 10: 1287–1289.

  • Scorrano L . (2005). J Bioenerg Biomembr 37: 165–170.

  • Scorrano L, Ashiya M, Buttle K, Weiler S, Oakes SA, Mannella CA et al. (2002). Dev Cell 2: 55–67.

  • Shaw JM, Nunnari J . (2002). Trends Cell Biol 12: 178–184.

  • Shimizu S, Mori N, Kishi M, Sugata H, Tsuda A, Kubota N . (2002). Jpn J Ophthalmol 46: 336–340.

  • Sik A, Passer BJ, Koonin EV, Pellegrini L . (2004). J Biol Chem 279: 15323–15329.

  • Smirnova E, Griparic L, Shurland DL, van der Bliek AM . (2001). Mol Biol Cell 12: 2245–2256.

  • Sugioka R, Shimizu S, Tsujimoto Y . (2004). J Biol Chem 279: 52726–52734.

  • Suzuki M, Jeong SY, Karbowski M, Youle RJ, Tjandra N . (2003). J Mol Biol 334: 445–458.

  • Szabadkai G, Simoni AM, Chami M, Wieckowski MR, Youle RJ, Rizzuto R . (2004). Mol Cell 16: 59–68.

  • Thiselton DL, Alexander C, Morris A, Brooks S, Rosenberg T, Eiberg H et al. (2001). Hum Genet 109: 498–502.

  • Thiselton DL, Alexander C, Taanman JW, Brooks S, Rosenberg T, Eiberg H et al. (2002). Invest Ophthalmol Vis Sci 43: 1715–1724.

  • Toomes C, Marchbank NJ, Mackey DA, Craig JE, Newbury-Ecob RA, Bennett CP et al. (2001). Hum Mol Genet 10: 1369–1378.

  • Varadi A, Johnson-Cadwell LI, Cirulli V, Yoon Y, Allan VJ, Rutter GA . (2004). J Cell Sci 117: 4389–4400.

  • Yaffe MP . (1999). Science 283: 1493–1497.

  • Yoon Y, Krueger EW, Oswald BJ, McNiven MA . (2003). Mol Cell Biol 23: 5409–5420.

  • Yoon Y, Pitts KR, McNiven MA . (2001). Mol Biol Cell 12: 2894–2905.

  • Youle RJ, Karbowski M . (2005). Nat Rev Mol Cell Biol 6: 657–663.

  • Yu TZ, Fox RJ, Burwell LS, Yoon Y . (2005). J Cell Sci 118: 4141–4151.

  • Zhang P, Hinshaw JE . (2001). Nat Cell Biol 3: 922–926.

  • Zuchner S, Mersiyanova IV, Muglia M, Bissar-Tadmouri N, Rochelle J, Dadali EL et al. (2004). Nat Genet 36: 449–451.

Download references

Acknowledgements

LS is an assistant Telethon scientist of the Dulbecco-Telethon Institute, and research in his laboratory is supported by Telethon Italy, AIRC Italy, Compagnia di San Paolo, Human Frontier Science Program Organization, UMDF. GMC was supported by a Fellowship for Perspective Researchers of the Swiss National Foundation.

Author information

Authors and Affiliations

  1. Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, Padova, Italy

    G M Cereghetti & L Scorrano

Authors
  1. G M Cereghetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L Scorrano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L Scorrano.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cereghetti, G., Scorrano, L. The many shapes of mitochondrial death. Oncogene 25, 4717–4724 (2006). https://doi.org/10.1038/sj.onc.1209605

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1209605

Keywords

This article is cited by

Search

Advanced search

Quick links