Mitochondria, play an important role in a variety of processes including energy production, apoptosis, autophagy and inflammation. Caspases, are proteases that play an essential role in mediating apoptotic process of programmed cell death. An association between mitochondria and caspases is very well defined during apoptosis. Besides apoptosis, emerging data is strongly suggesting a direct association between mitochondria and caspases in regulation of a variety of non-apoptotic processes such as mitochondrial dynamics, autophagy, mitochondrial membrane permeabilization, immune responses and differentiation. On one hand mitochondria regulate activation and localization of caspases, caspases also regulate mitochondrial function, thus a feedback loop exist between mitochondria and caspases to regulate a variety of processes. In this review, we have focused on interaction between caspases and mitochondria in the regulation of each other for mediating a variety of apoptotic and non-apoptotic functions. Since both mitochondria and caspases play an important role in development of a variety of diseases like cancer, neurodegeneration, immune disorders, accelerated aging; understanding association between the two will pave the way for better understanding and designing the therapeutics modalities for a variety of diseases. This review is a part of special issue on mitochondria: implication in human health and diseases.
Lokendra Kumar Sharma,
Ajit K. Saxena,
Madan M. Godbole,
Interaction Between Mitochondria and Caspases: Apoptotic and Non-Apoptotic Roles, Cell Biology. Special Issue: Mitochondria: Implications in Human Health and Diseases.
Vol. 3, No. 2-1,
2015, pp. 22-30.
J. Nunnari, A. Suomalainen, Mitochondria: in sickness and in health, Cell, 148 (2012) 1145-1159.
M.J. Goldenthal, J. Marin-Garcia, Mitochondrial signaling pathways: a receiver/integrator organelle, Molecular and cellular biochemistry, 262 (2004) 1-16.
D.R. McIlwain, T. Berger, T.W. Mak, Caspase functions in cell death and disease, Cold Spring Harbor perspectives in biology, 5 (2013) a008656.
A. Thorburn, Apoptosis and autophagy: regulatory connections between two supposedly different processes, Apoptosis : an international journal on programmed cell death, 13 (2008) 1-9.
N.A. Thornberry, Y. Lazebnik, Caspases: enemies within, Science, 281 (1998) 1312-1316.
S.P. Cullen, S.J. Martin, Caspase activation pathways: some recent progress, Cell death and differentiation, 16 (2009) 935-938.
J. Li, J. Yuan, Caspases in apoptosis and beyond, Oncogene, 27 (2008) 6194-6206.
S. Elmore, Apoptosis: a review of programmed cell death, Toxicologic pathology, 35 (2007) 495-516.
B. Fadeel, S. Orrenius, Apoptosis: a basic biological phenomenon with wide-ranging implications in human disease, Journal of internal medicine, 258 (2005) 479-517.
C.M. Rudin, C.B. Thompson, Apoptosis and disease: regulation and clinical relevance of programmed cell death, Annual review of medicine, 48 (1997) 267-281.
S.W. Tait, D.R. Green, Caspase-independent cell death: leaving the set without the final cut, Oncogene, 27 (2008) 6452-6461.
M. Nguyen, D.G. Millar, V.W. Yong, S.J. Korsmeyer, G.C. Shore, Targeting of Bcl-2 to the mitochondrial outer membrane by a COOH-terminal signal anchor sequence, The Journal of biological chemistry, 268 (1993) 25265-25268.
D.D. Newmeyer, D.M. Farschon, J.C. Reed, Cell-free apoptosis in Xenopus egg extracts: inhibition by Bcl-2 and requirement for an organelle fraction enriched in mitochondria, Cell, 79 (1994) 353-364.
N.J. Waterhouse, J.E. Ricci, D.R. Green, And all of a sudden it's over: mitochondrial outer-membrane permeabilization in apoptosis, Biochimie, 84 (2002) 113-121.
M.M. Cleland, K.L. Norris, M. Karbowski, C. Wang, D.F. Suen, S. Jiao, N.M. George, X. Luo, Z. Li, R.J. Youle, Bcl-2 family interaction with the mitochondrial morphogenesis machinery, Cell death and differentiation, 18 (2011) 235-247.
S.G. Rolland, B. Conradt, New role of the BCL2 family of proteins in the regulation of mitochondrial dynamics, Current opinion in cell biology, 22 (2010) 852-858.
W.W. Wong, H. Puthalakath, Bcl-2 family proteins: the sentinels of the mitochondrial apoptosis pathway, IUBMB life, 60 (2008) 390-397.
M. van Gurp, N. Festjens, G. van Loo, X. Saelens, P. Vandenabeele, Mitochondrial intermembrane proteins in cell death, Biochemical and biophysical research communications, 304 (2003) 487-497.
H. Li, H. Zhu, C.J. Xu, J. Yuan, Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis, Cell, 94 (1998) 491-501.
G. Krumschnabel, B. Sohm, F. Bock, C. Manzl, A. Villunger, The enigma of caspase-2: the laymen's view, Cell death and differentiation, 16 (2009) 195-207.
M. Tiwari, M. Lopez-Cruzan, W.W. Morgan, B. Herman, Loss of caspase-2-dependent apoptosis induces autophagy after mitochondrial oxidative stress in primary cultures of young adult cortical neurons, The Journal of biological chemistry, 286 (2011) 8493-8506.
J.C. Means, I. Muro, R.J. Clem, Lack of involvement of mitochondrial factors in caspase activation in a Drosophila cell-free system, Cell death and differentiation, 13 (2006) 1222-1234.
B. Zhivotovsky, A. Samali, A. Gahm, S. Orrenius, Caspases: their intracellular localization and translocation during apoptosis, Cell death and differentiation, 6 (1999) 644-651.
S. Krajewski, M. Krajewska, L.M. Ellerby, K. Welsh, Z. Xie, Q.L. Deveraux, G.S. Salvesen, D.E. Bredesen, R.E. Rosenthal, G. Fiskum, J.C. Reed, Release of caspase-9 from mitochondria during neuronal apoptosis and cerebral ischemia, Proceedings of the National Academy of Sciences of the United States of America, 96 (1999) 5752-5757.
M. Mancini, D.W. Nicholson, S. Roy, N.A. Thornberry, E.P. Peterson, L.A. Casciola-Rosen, A. Rosen, The caspase-3 precursor has a cytosolic and mitochondrial distribution: implications for apoptotic signaling, The Journal of cell biology, 140 (1998) 1485-1495.
Z.H. Qin, Y. Wang, K.K. Kikly, E. Sapp, K.B. Kegel, N. Aronin, M. DiFiglia, Pro-caspase-8 is predominantly localized in mitochondria and released into cytoplasm upon apoptotic stimulation, The Journal of biological chemistry, 276 (2001) 8079-8086.
A. Samali, B. Zhivotovsky, D.P. Jones, S. Orrenius, Detection of pro-caspase-3 in cytosol and mitochondria of various tissues, FEBS letters, 431 (1998) 167-169.
K.C. Zimmermann, N.J. Waterhouse, J.C. Goldstein, M. Schuler, D.R. Green, Aspirin induces apoptosis through release of cytochrome c from mitochondria, Neoplasia, 2 (2000) 505-513.
M. Mancini, C.E. Machamer, S. Roy, D.W. Nicholson, N.A. Thornberry, L.A. Casciola-Rosen, A. Rosen, Caspase-2 is localized at the Golgi complex and cleaves golgin-160 during apoptosis, The Journal of cell biology, 149 (2000) 603-612.
S.A. Susin, H.K. Lorenzo, N. Zamzami, I. Marzo, C. Brenner, N. Larochette, M.C. Prevost, P.M. Alzari, G. Kroemer, Mitochondrial release of caspase-2 and -9 during the apoptotic process, The Journal of experimental medicine, 189 (1999) 381-394.
G. van Loo, X. Saelens, F. Matthijssens, P. Schotte, R. Beyaert, W. Declercq, P. Vandenabeele, Caspases are not localized in mitochondria during life or death, Cell death and differentiation, 9 (2002) 1207-1211.
D. Chandra, D.G. Tang, Mitochondrially localized active caspase-9 and caspase-3 result mostly from translocation from the cytosol and partly from caspase-mediated activation in the organelle. Lack of evidence for Apaf-1-mediated procaspase-9 activation in the mitochondria, The Journal of biological chemistry, 278 (2003) 17408-17420.
F. Gonzalvez, Z.T. Schug, R.H. Houtkooper, E.D. MacKenzie, D.G. Brooks, R.J. Wanders, P.X. Petit, F.M. Vaz, E. Gottlieb, Cardiolipin provides an essential activating platform for caspase-8 on mitochondria, The Journal of cell biology, 183 (2008) 681-696.
B. Gajkowska, U. Wojewodzka, J. Gajda, Translocation of Bax and Bid to mitochondria, endoplasmic reticulum and nuclear envelope: possible control points in apoptosis, Journal of molecular histology, 35 (2004) 11-19.
N. Mizushima, Autophagy: process and function, Genes & development, 21 (2007) 2861-2873.
M. Graef, J. Nunnari, A role for mitochondria in autophagy regulation, Autophagy, 7 (2011) 1245-1246.
Y. Chen, D.J. Klionsky, The regulation of autophagy - unanswered questions, Journal of cell science, 124 (2011) 161-170.
L. Yu, M.J. Lenardo, E.H. Baehrecke, Autophagy and caspases: a new cell death program, Cell cycle, 3 (2004) 1124-1126.
M. Tiwari, L.K. Sharma, D. Vanegas, D.A. Callaway, Y. Bai, J.D. Lechleiter, B. Herman, A nonapoptotic role for CASP2/caspase 2: modulation of autophagy, Autophagy, 10 (2014) 1054-1070.
M. Tiwari, V.K. Bajpai, A.A. Sahasrabuddhe, A. Kumar, R.A. Sinha, S. Behari, M.M. Godbole, Inhibition of N-(4-hydroxyphenyl)retinamide-induced autophagy at a lower dose enhances cell death in malignant glioma cells, Carcinogenesis, 29 (2008) 600-609.
L. DeVorkin, N.E. Go, Y.C. Hou, A. Moradian, G.B. Morin, S.M. Gorski, The Drosophila effector caspase Dcp-1 regulates mitochondrial dynamics and autophagic flux via SesB, The Journal of cell biology, 205 (2014) 477-492.
Q. Sun, W. Gao, P. Loughran, R. Shapiro, J. Fan, T.R. Billiar, M.J. Scott, Caspase 1 activation is protective against hepatocyte cell death by up-regulating beclin 1 protein and mitochondrial autophagy in the setting of redox stress, The Journal of biological chemistry, 288 (2013) 15947-15958.
H.S. Jeong, H.Y. Choi, E.R. Lee, J.H. Kim, K. Jeon, H.J. Lee, S.G. Cho, Involvement of caspase-9 in autophagy-mediated cell survival pathway, Biochimica et biophysica acta, 1813 (2011) 80-90.
E. Wirawan, L. Vande Walle, K. Kersse, S. Cornelis, S. Claerhout, I. Vanoverberghe, R. Roelandt, R. De Rycke, J. Verspurten, W. Declercq, P. Agostinis, T. Vanden Berghe, S. Lippens, P. Vandenabeele, Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria, Cell death & disease, 1 (2010) e18.
J. Yu, H. Nagasu, T. Murakami, H. Hoang, L. Broderick, H.M. Hoffman, T. Horng, Inflammasome activation leads to Caspase-1-dependent mitochondrial damage and block of mitophagy, Proceedings of the National Academy of Sciences of the United States of America, 111 (2014) 15514-15519.
D.C. Chan, Mitochondrial fusion and fission in mammals, Annual review of cell and developmental biology, 22 (2006) 79-99.
S.Y. Jeong, D.W. Seol, The role of mitochondria in apoptosis, BMB reports, 41 (2008) 11-22.
J. Li, J. Zhou, Y. Li, D. Qin, P. Li, Mitochondrial fission controls DNA fragmentation by regulating endonuclease G, Free radical biology & medicine, 49 (2010) 622-631.
J.Y. Peng, C.C. Lin, Y.J. Chen, L.S. Kao, Y.C. Liu, C.C. Chou, Y.H. Huang, F.R. Chang, Y.C. Wu, Y.S. Tsai, C.N. Hsu, Automatic morphological subtyping reveals new roles of caspases in mitochondrial dynamics, PLoS computational biology, 7 (2011) e1002212.
D.G. Kirsch, A. Doseff, B.N. Chau, D.S. Lim, N.C. de Souza-Pinto, R. Hansford, M.B. Kastan, Y.A. Lazebnik, J.M. Hardwick, Caspase-3-dependent cleavage of Bcl-2 promotes release of cytochrome c, The Journal of biological chemistry, 274 (1999) 21155-21161.
C. Sheridan, S.J. Martin, Mitochondrial fission/fusion dynamics and apoptosis, Mitochondrion, 10 (2010) 640-648.
C. Voisine, E.A. Craig, N. Zufall, O. von Ahsen, N. Pfanner, W. Voos, The protein import motor of mitochondria: unfolding and trapping of preproteins are distinct and separable functions of matrix Hsp70, Cell, 97 (1999) 565-574.
T. Kuwana, M.R. Mackey, G. Perkins, M.H. Ellisman, M. Latterich, R. Schneiter, D.R. Green, D.D. Newmeyer, Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane, Cell, 111 (2002) 331-342.
N.J. Waterhouse, J.C. Goldstein, O. von Ahsen, M. Schuler, D.D. Newmeyer, D.R. Green, Cytochrome c maintains mitochondrial transmembrane potential and ATP generation after outer mitochondrial membrane permeabilization during the apoptotic process, The Journal of cell biology, 153 (2001) 319-328.
E. Bossy-Wetzel, D.D. Newmeyer, D.R. Green, Mitochondrial cytochrome c release in apoptosis occurs upstream of DEVD-specific caspase activation and independently of mitochondrial transmembrane depolarization, The EMBO journal, 17 (1998) 37-49.
M. Deshmukh, K. Kuida, E.M. Johnson, Jr., Caspase inhibition extends the commitment to neuronal death beyond cytochrome c release to the point of mitochondrial depolarization, The Journal of cell biology, 150 (2000) 131-143.
J.C. Goldstein, N.J. Waterhouse, P. Juin, G.I. Evan, D.R. Green, The coordinate release of cytochrome c during apoptosis is rapid, complete and kinetically invariant, Nature cell biology, 2 (2000) 156-162.
E. Cepero, A.M. King, L.M. Coffey, R.G. Perez, L.H. Boise, Caspase-9 and effector caspases have sequential and distinct effects on mitochondria, Oncogene, 24 (2005) 6354-6366.
M. Brentnall, L. Rodriguez-Menocal, R.L. De Guevara, E. Cepero, L.H. Boise, Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis, BMC cell biology, 14 (2013) 32.
F. Martinon, J. Tschopp, Inflammatory caspases: linking an intracellular innate immune system to autoinflammatory diseases, Cell, 117 (2004) 561-574.
M.A. Walker, S. Volpi, K.B. Sims, J.E. Walter, E. Traggiai, Powering the immune system: mitochondria in immune function and deficiency, Journal of immunology research, 2014 (2014) 164309.
J. Tschopp, Mitochondria: Sovereign of inflammation?, European journal of immunology, 41 (2011) 1196-1202.
L. Galluzzi, O. Kepp, G. Kroemer, Mitochondria: master regulators of danger signalling, Nature reviews. Molecular cell biology, 13 (2012) 780-788.
R. Zhou, A. Tardivel, B. Thorens, I. Choi, J. Tschopp, Thioredoxin-interacting protein links oxidative stress to inflammasome activation, Nature immunology, 11 (2010) 136-140.
G. Kroemer, L. Galluzzi, O. Kepp, L. Zitvogel, Immunogenic cell death in cancer therapy, Annual review of immunology, 31 (2013) 51-72.
A. Rongvaux, R. Jackson, C.C. Harman, T. Li, A.P. West, M.R. de Zoete, Y. Wu, B. Yordy, S.A. Lakhani, C.Y. Kuan, T. Taniguchi, G.S. Shadel, Z.J. Chen, A. Iwasaki, R.A. Flavell, Apoptotic caspases prevent the induction of type I interferons by mitochondrial DNA, Cell, 159 (2014) 1563-1577.
D.B. Stetson, R. Medzhitov, Type I interferons in host defense, Immunity, 25 (2006) 373-381.
S. El Maadidi, L. Faletti, B. Berg, C. Wenzl, K. Wieland, Z.J. Chen, U. Maurer, C. Borner, A novel mitochondrial MAVS/Caspase-8 platform links RNA virus-induced innate antiviral signaling to Bax/Bak-independent apoptosis, Journal of immunology, 192 (2014) 1171-1183.
M. Miura, Apoptotic and nonapoptotic caspase functions in animal development, Cold Spring Harbor perspectives in biology, 4 (2012).
R. Dahm, Lens fibre cell differentiation - A link with apoptosis?, Ophthalmic research, 31 (1999) 163-183.
S. Lippens, M. Kockx, M. Knaapen, L. Mortier, R. Polakowska, A. Verheyen, M. Garmyn, A. Zwijsen, P. Formstecher, D. Huylebroeck, P. Vandenabeele, W. Declercq, Epidermal differentiation does not involve the pro-apoptotic executioner caspases, but is associated with caspase-14 induction and processing, Cell death and differentiation, 7 (2000) 1218-1224.
A. Shcherbina, E. Remold-O'Donnell, Role of caspase in a subset of human platelet activation responses, Blood, 93 (1999) 4222-4231.
Y. Zermati, C. Garrido, S. Amsellem, S. Fishelson, D. Bouscary, F. Valensi, B. Varet, E. Solary, O. Hermine, Caspase activation is required for terminal erythroid differentiation, The Journal of experimental medicine, 193 (2001) 247-254.
A. Kasahara, L. Scorrano, Mitochondria: from cell death executioners to regulators of cell differentiation, Trends in cell biology, 24 (2014) 761-770.
T.V. Murray, J.M. McMahon, B.A. Howley, A. Stanley, T. Ritter, A. Mohr, R. Zwacka, H.O. Fearnhead, A non-apoptotic role for caspase-9 in muscle differentiation, Journal of cell science, 121 (2008) 3786-3793.
C. Allombert-Blaise, S. Tamiji, L. Mortier, H. Fauvel, M. Tual, E. Delaporte, F. Piette, E.M. DeLassale, P. Formstecher, P. Marchetti, R. Polakowska, Terminal differentiation of human epidermal keratinocytes involves mitochondria- and caspase-dependent cell death pathway, Cell death and differentiation, 10 (2003) 850-852.
E.J. Sanders, E. Parker, The role of mitochondria, cytochrome c and caspase-9 in embryonic lens fibre cell denucleation, Journal of anatomy, 201 (2002) 121-135.
O. Sordet, C. Rebe, S. Plenchette, Y. Zermati, O. Hermine, W. Vainchenker, C. Garrido, E. Solary, L. Dubrez-Daloz, Specific involvement of caspases in the differentiation of monocytes into macrophages, Blood, 100 (2002) 4446-4453.
E. Arama, J. Agapite, H. Steller, Caspase activity and a specific cytochrome C are required for sperm differentiation in Drosophila, Developmental cell, 4 (2003) 687-697.