Apaf1 inhibition promotes cell recovery from apoptosis

Anna Gortat , Mónica Sancho , Laura Mondragón , Àgel Messeguer , Enrique Pérez-Payá , Mar Orzáez

Protein Cell ›› 2015, Vol. 6 ›› Issue (11) : 833 -843.

PDF (1791KB)
Protein Cell ›› 2015, Vol. 6 ›› Issue (11) : 833 -843. DOI: 10.1007/s13238-015-0200-2
RESEARCH ARTICLE
RESEARCH ARTICLE

Apaf1 inhibition promotes cell recovery from apoptosis

Author information +
History +
PDF (1791KB)

Abstract

The protein apoptotic protease activating factor 1 (Apaf1) is the central component of the apoptosome, a multiprotein complex that activates procaspase-9 after cytochrome c release from the mitochondria in the intrinsic pathway of apoptosis. We have developed a vital method that allows fluorescence-activated cell sorting of cells at different stages of the apoptotic pathway and demonstrated that upon pharmacological inhibition of Apaf1, cells recover from doxorubicin- or hypoxia-induced early apoptosis to normal healthy cell. Inhibiting Apaf1 not only prevents procaspase-9 activation but delays massive mitochondrial damage allowing cell recovery.

Keywords

Apaf1 / Apaf1 inhibitors / apoptosis / apoptosome / autophagy / cell recovery

Cite this article

Download citation ▾
Anna Gortat, Mónica Sancho, Laura Mondragón, Àgel Messeguer, Enrique Pérez-Payá, Mar Orzáez. Apaf1 inhibition promotes cell recovery from apoptosis. Protein Cell, 2015, 6(11): 833-843 DOI:10.1007/s13238-015-0200-2

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Albeck JG, Burke JM, Aldridge BB, Zhang M, Lauffenburger DA, Sorger PK (2008) Quantitative analysis of pathways controlling extrinsic apoptosis in single cells. Mol Cell 30: 11−25

[2]

Andreu-Fernandez V, Genoves A, Messeguer A, Orzaez M, Sancho M, Perez-Paya E (2013) BH3-mimetics- and cisplatin-induced cell death proceeds through different pathways depending on the availability of death-related cellular components. PLoS One 8: e56881

[3]

Boya P, Gonzalez-Polo RA, Casares N, Perfettini JL, Dessen P, Larochette N, Metivier D, Meley D, Souquere S, Yoshimori T (2005) Inhibition of macroautophagy triggers apoptosis. Mol Cell Biol 25: 1025−1040

[4]

Brenner D, Mak TW (2009) Mitochondrial cell death effectors. Curr Opin Cell Biol 21: 871−877

[5]

Cheng Y, Deshmukh M, D’Costa A, Demaro JA, Gidday JM, Shah A, Sun Y, Jacquin MF, Johnson EM, Holtzman DM (1998) Caspase inhibitor affords neuroprotection with delayed administration in a rat model of neonatal hypoxic-ischemic brain injury. J Clin Invest 101: 1992−1999

[6]

Colell A, Ricci JE, Tait S, Milasta S, Maurer U, Bouchier-Hayes L, Fitzgerald P, Guio-Carrion A, Waterhouse NJ, Li CW (2007) GAPDH and autophagy preserve survival after apoptotic cytochrome c release in the absence of caspase activation. Cell 129: 983−997

[7]

D’Amelio M, Cavallucci V, Middei S, Marchetti C, Pacioni S, Ferri A, Diamantini A, De Zio D, Carrara P, Battistini L (2011) Caspase-3 triggers early synaptic dysfunction in a mouse model of Alzheimer’s disease. Nat Neurosci 14: 69−76

[8]

Debatin KMFS (2006) Apoptosis and cancer therapy. WILEY-VCH, Weinheim

[9]

Deshmukh M, Kuida K, Johnson EM Jr (2000) Caspase inhibition extends the commitment to neuronal death beyond cytochrome c release to the point of mitochondrial depolarization. J Cell Biol 150: 131−143

[10]

Dignam JD, Lebovitz RM, Roeder RG (1983) Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res 11: 1475−1489

[11]

Fearnhead HO (2001) Cell-free systems to study apoptosis. Methods Cell Biol 66: 167−185

[12]

Ferraro E, Pulicati A, Cencioni MT, Cozzolino M, Navoni F, di Martino S, Nardacci R, Carri MT, Cecconi F (2008) Apoptosome-deficient cells lose cytochrome c through proteasomal degradation but survive by autophagy-dependent glycolysis. Mol Biol Cell 19: 3576−3588

[13]

Gao Y, Liang W, Hu X, Zhang W, Stetler RA, Vosler P, Cao G, Chen J (2009) Neuroprotection against hypoxic-ischemic brain injury by inhibiting the apoptotic protease activating factor-1 pathway. Stroke 41: 166−172

[14]

Green DR, Kroemer G (2005) Pharmacological manipulation of cell death: clinical applications in sight? J Clin Invest 115: 2610−2617

[15]

Hoeppner DJ, Hengartner MO, Schnabel R (2001) Engulfment genes cooperate with ced-3 to promote cell death in Caenorhabditis elegans<?Pub Caret?>. Nature 412: 202−206

[16]

Hoglen NC, Chen LS, Fisher CD, Hirakawa BP, Groessl T, Contreras PC (2004) Characterization of IDN-6556 (3-[2-(2-tert-butyl-phenylaminooxalyl)-amino]-propionylamino]-4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid): a liver-targeted caspase inhibitor. J Pharmacol Exp Ther 309: 634−640

[17]

Hotchkiss RS, Karl IE (2003) The pathophysiology and treatment of sepsis. N Engl J Med 348: 138−150

[18]

Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. Embo J 19: 5720−5728

[19]

Kabeya Y, Mizushima N, Yamamoto A, Oshitani-Okamoto S, Ohsumi Y, Yoshimori T (2004) LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation. J Cell Sci 117: 2805−2812

[20]

Kunstle G, Leist M, Uhlig S, Revesz L, Feifel R, MacKenzie A, Wendel A (1997) ICE-protease inhibitors block murine liver injury and apoptosis caused by CD95 or by TNF-alpha. Immunol Lett 55: 5−10

[21]

Linton SD (2005) Caspase inhibitors: a pharmaceutical industry perspective. Curr Top Med Chem 5: 1697−1717

[22]

MacFarlane M, Merrison W, Bratton SB, Cohen GM (2002) Proteasome-mediated degradation of Smac during apoptosis: XIAP promotes Smac ubiquitination in vitro. J Biol Chem 277: 36611−36616

[23]

Madeo F, Tavernarakis N, Kroemer G (2010) Can autophagy promote longevity? Nat Cell Biol 12: 842−846

[24]

Malet G, Martin AG, Orzaez M, Vicent MJ, Masip I, Sanclimens G, Ferrer-Montiel A, Mingarro I, Messeguer A, Fearnhead HO (2006) Small molecule inhibitors of Apaf-1-related caspase- 3/-9 activation that control mitochondrial-dependent apoptosis. Cell Death Differ 13: 1523−1532

[25]

Martinou I, Desagher S, Eskes R, Antonsson B, Andre E, Fakan S, Martinou JC (1999) The release of cytochrome c from mitochondria during apoptosis of NGF-deprived sympathetic neurons is a reversible event. J Cell Biol 144: 883−889

RIGHTS & PERMISSIONS

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

AI Summary AI Mindmap
PDF (1791KB)

Supplementary files

PAC-0833-15057-OM_suppl_1

1047

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/