Spatial and temporal association of Bax with mitochondrial fission sites, Drp1, and Mfn2 during apoptosis

doi:10.1083/jcb.200209124

Published 23 December 2002. doi:10.1083/jcb.200209124

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© The Rockefeller University Press, 0021-9525/2002/12/931 $5.00
The Journal of Cell Biology, Volume 159, Number 6, 931-938

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Spatial and temporal association of Bax with mitochondrial fission sites, Drp1, and Mfn2 during apoptosis

Mariusz Karbowski¹, Yang-Ja Lee¹, Brigitte Gaume¹, Seon-Yong Jeong¹, Stephan Frank¹, Amotz Nechushtan¹, Ansgar Santel³, Margaret Fuller³, Carolyn L. Smith² and Richard J. Youle¹

¹ Biochemistry Section, SNB
² Light Imaging Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892
³ Department of Developmental Biology, Stanford University School of Medicine, Palo Alto, CA 94305

Address correspondence to Richard Youle, Building 10, Room 5D-37, National Institutes of Health, BSSNB, 10 Center Drive, MSC 1414, Bethesda, MD 20892. Tel.: (301) 496-6628. Fax: (301) 402-0380. E-mail: youle{at}helix.nih.gov

We find that Bax, a proapoptotic member of the Bcl-2 family,translocates to discrete foci on mitochondria during the initialstages of apoptosis, which subsequently become mitochondrialscission sites. A dominant negative mutant of Drp1, Drp1^K38A,inhibits apoptotic scission of mitochondria, but does not inhibitBax translocation or coalescence into foci. However, Drp1^K38Acauses the accumulation of mitochondrial fission intermediatesthat are associated with clusters of Bax. Surprisingly, Drp1and Mfn2, but not other proteins implicated in the regulationof mitochondrial morphology, colocalize with Bax in these foci.We suggest that Bax participates in apoptotic fragmentationof mitochondria.

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Norris, K. L., Youle, R. J. (2008). Cytomegalovirus Proteins vMIA and m38.5 Link Mitochondrial Morphogenesis to Bcl-2 Family Proteins. J. Virol. 82: 6232-6243 [Abstract] [Full Text]
Suen, D.-F., Norris, K. L., Youle, R. J. (2008). Mitochondrial dynamics and apoptosis. Genes Dev. 22: 1577-1590 [Abstract] [Full Text]
Germain, M., Milburn, J., Duronio, V. (2008). MCL-1 Inhibits BAX in the Absence of MCL-1/BAX Interaction. J. Biol. Chem. 283: 6384-6392 [Abstract] [Full Text]
Gustafsson, A. B., Gottlieb, R. A. (2008). Heart mitochondria: gates of life and death. Cardiovasc Res 77: 334-343 [Abstract] [Full Text]
Arismendi-Morillo, G. J., Castellano-Ramirez, A. V. (2008). Ultrastructural mitochondrial pathology in human astrocytic tumors: potentials implications pro-therapeutics strategies. J Electron Microsc (Tokyo) 57: 33-39 [Abstract] [Full Text]
Wu, L., Li, Z., Zhang, Y., Zhang, P., Zhu, X., Huang, J., Ma, T., Lu, T., Song, Q., Li, Q., Guo, Y., Tang, J., Ma, D., Chen, K.-H., Qiu, X. (2008). Adenovirus-expressed human hyperplasia suppressor gene induces apoptosis in cancer cells. Molecular Cancer Therapeutics 7: 222-232 [Abstract] [Full Text]
Zeidan, Y. H., Wu, B. X., Jenkins, R. W., Obeid, L. M., Hannun, Y. A. (2008). A novel role for protein kinase C{delta}-mediated phosphorylation of acid sphingomyelinase in UV light-induced mitochondrial injury. FASEB J. 22: 183-193 [Abstract] [Full Text]
Kwong, J. Q., Henning, M. S., Starkov, A. A., Manfredi, G. (2007). The mitochondrial respiratory chain is a modulator of apoptosis. JCB 179: 1163-1177 [Abstract] [Full Text]
Gillissen, B., Essmann, F., Hemmati, P. G., Richter, A., Richter, A., Oztop, I., Chinnadurai, G., Dorken, B., Daniel, P. T. (2007). Mcl-1 determines the Bax dependency of Nbk/Bik-induced apoptosis. JCB 179: 701-715 [Abstract] [Full Text]
Wells, R. C., Picton, L. K., Williams, S. C. P., Tan, F. J., Hill, R. B. (2007). Direct Binding of the Dynamin-like GTPase, Dnm1, to Mitochondrial Dynamics Protein Fis1 Is Negatively Regulated by the Fis1 N-terminal Arm. J. Biol. Chem. 282: 33769-33775 [Abstract] [Full Text]
Bras, M., Yuste, V. J., Roue, G., Barbier, S., Sancho, P., Virely, C., Rubio, M., Baudet, S., Esquerda, J. E., Merle-Beral, H., Sarfati, M., Susin, S. A. (2007). Drp1 Mediates Caspase-Independent Type III Cell Death in Normal and Leukemic Cells. Mol. Cell. Biol. 27: 7073-7088 [Abstract] [Full Text]
Karbowski, M., Neutzner, A., Youle, R. J. (2007). The mitochondrial E3 ubiquitin ligase MARCH5 is required for Drp1 dependent mitochondrial division. JCB 178: 71-84 [Abstract] [Full Text]
Duvezin-Caubet, S., Koppen, M., Wagener, J., Zick, M., Israel, L., Bernacchia, A., Jagasia, R., Rugarli, E. I., Imhof, A., Neupert, W., Langer, T., Reichert, A. S. (2007). OPA1 Processing Reconstituted in Yeast Depends on the Subunit Composition of the m-AAA Protease in Mitochondria. Mol. Biol. Cell 18: 3582-3590 [Abstract] [Full Text]
Jahani-Asl, A., Cheung, E. C. C., Neuspiel, M., MacLaurin, J. G., Fortin, A., Park, D. S., McBride, H. M., Slack, R. S. (2007). Mitofusin 2 Protects Cerebellar Granule Neurons against Injury-induced Cell Death. J. Biol. Chem. 282: 23788-23798 [Abstract] [Full Text]
Shen, T., Zheng, M., Cao, C., Chen, C., Tang, J., Zhang, W., Cheng, H., Chen, K.-H., Xiao, R.-P. (2007). Mitofusin-2 Is a Major Determinant of Oxidative Stress-mediated Heart Muscle Cell Apoptosis. J. Biol. Chem. 282: 23354-23361 [Abstract] [Full Text]
Lee, S., Jeong, S.-Y., Lim, W.-C., Kim, S., Park, Y.-Y., Sun, X., Youle, R. J., Cho, H. (2007). Mitochondrial Fission and Fusion Mediators, hFis1 and OPA1, Modulate Cellular Senescence. J. Biol. Chem. 282: 22977-22983 [Abstract] [Full Text]
Brooks, C., Wei, Q., Feng, L., Dong, G., Tao, Y., Mei, L., Xie, Z.-J., Dong, Z. (2007). Bak regulates mitochondrial morphology and pathology during apoptosis by interacting with mitofusins. Proc. Natl. Acad. Sci. USA 104: 11649-11654 [Abstract] [Full Text]
Wasiak, S., Zunino, R., McBride, H. M. (2007). Bax/Bak promote sumoylation of DRP1 and its stable association with mitochondria during apoptotic cell death. JCB 177: 439-450 [Abstract] [Full Text]
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Gustafsson, A. B., Gottlieb, R. A. (2007). Bcl-2 family members and apoptosis, taken to heart. Am. J. Physiol. Cell Physiol. 292: C45-C51 [Abstract] [Full Text]
Duvezin-Caubet, S., Jagasia, R., Wagener, J., Hofmann, S., Trifunovic, A., Hansson, A., Chomyn, A., Bauer, M. F., Attardi, G., Larsson, N.-G., Neupert, W., Reichert, A. S. (2006). Proteolytic Processing of OPA1 Links Mitochondrial Dysfunction to Alterations in Mitochondrial Morphology. J. Biol. Chem. 281: 37972-37979 [Abstract] [Full Text]
Ying, S., Fischer, S. F., Pettengill, M., Conte, D., Paschen, S. A., Ojcius, D. M., Hacker, G. (2006). Characterization of Host Cell Death Induced by Chlamydia trachomatis. Infect. Immun. 74: 6057-6066 [Abstract] [Full Text]
Alirol, E., James, D., Huber, D., Marchetto, A., Vergani, L., Martinou, J.-C., Scorrano, L. (2006). The Mitochondrial Fission Protein hFis1 Requires the Endoplasmic Reticulum Gateway to Induce Apoptosis. Mol. Biol. Cell 17: 4593-4605 [Abstract] [Full Text]
Poncet, D., Pauleau, A.-L., Szabadkai, G., Vozza, A., Scholz, S. R., Le Bras, M., Briere, J.-J., Jalil, A., Le Moigne, R., Brenner, C., Hahn, G., Wittig, I., Schagger, H., Lemaire, C., Bianchi, K., Souquere, S., Pierron, G., Rustin, P., Goldmacher, V. S., Rizzuto, R., Palmieri, F., Kroemer, G. (2006). Cytopathic effects of the cytomegalovirus-encoded apoptosis inhibitory protein vMIA. JCB 174: 985-996 [Abstract] [Full Text]
Aleo, E., Henderson, C. J., Fontanini, A., Solazzo, B., Brancolini, C. (2006). Identification of new compounds that trigger apoptosome-independent caspase activation and apoptosis.. Cancer Res. 66: 9235-9244 [Abstract] [Full Text]
Dimmer, K. S., Scorrano, L. (2006). (De)constructing Mitochondria: What For?. Physiology 21: 233-241 [Abstract] [Full Text]
Logan, D. C. (2006). The mitochondrial compartment. J Exp Bot 57: 1225-1243 [Abstract] [Full Text]
Su, J., Wang, G., Barrett, J. W., Irvine, T. S., Gao, X., McFadden, G. (2006). Myxoma Virus M11L Blocks Apoptosis through Inhibition of Conformational Activation of Bax at the Mitochondria. J. Virol. 80: 1140-1151 [Abstract] [Full Text]
Tikhomirov, O., Carpenter, G. (2005). Bax activation and translocation to mitochondria mediate EGF-induced programmed cell death. J. Cell Sci. 118: 5681-5690 [Abstract] [Full Text]
Takahashi, Y., Karbowski, M., Yamaguchi, H., Kazi, A., Wu, J., Sebti, S. M., Youle, R. J., Wang, H.-G. (2005). Loss of Bif-1 Suppresses Bax/Bak Conformational Change and Mitochondrial Apoptosis. Mol. Cell. Biol. 25: 9369-9382 [Abstract] [Full Text]
Arnoult, D., Grodet, A., Lee, Y.-J., Estaquier, J., Blackstone, C. (2005). Release of OPA1 during Apoptosis Participates in the Rapid and Complete Release of Cytochrome c and Subsequent Mitochondrial Fragmentation. J. Biol. Chem. 280: 35742-35750 [Abstract] [Full Text]
Chen, H., Chan, D. C. (2005). Emerging functions of mammalian mitochondrial fusion and fission. Hum Mol Genet 14: R283-R289 [Abstract] [Full Text]
Lee, V. Y., Schroedl, C., Brunelle, J. K., Buccellato, L. J., Akinci, O. I., Kaneto, H., Snyder, C., Eisenbart, J., Budinger, G. R. S., Chandel, N. S. (2005). Bleomycin induces alveolar epithelial cell death through JNK-dependent activation of the mitochondrial death pathway. Am. J. Physiol. Lung Cell. Mol. Physiol. 289: L521-L528 [Abstract] [Full Text]
Yu, T., Fox, R. J., Burwell, L. S., Yoon, Y. (2005). Regulation of mitochondrial fission and apoptosis by the mitochondrial outer membrane protein hFis1. J. Cell Sci. 118: 4141-4151 [Abstract] [Full Text]
Tondera, D., Czauderna, F., Paulick, K., Schwarzer, R., Kaufmann, J., Santel, A. (2005). The mitochondrial protein MTP18 contributes to mitochondrial fission in mammalian cells. J. Cell Sci. 118: 3049-3059 [Abstract] [Full Text]
Neuspiel, M., Zunino, R., Gangaraju, S., Rippstein, P., McBride, H. (2005). Activated Mitofusin 2 Signals Mitochondrial Fusion, Interferes with Bax Activation, and Reduces Susceptibility to Radical Induced Depolarization. J. Biol. Chem. 280: 25060-25070 [Abstract] [Full Text]
Mathai, J. P., Germain, M., Shore, G. C. (2005). BH3-only BIK Regulates BAX,BAK-dependent Release of Ca2+ from Endoplasmic Reticulum Stores and Mitochondrial Apoptosis during Stress-induced Cell Death. J. Biol. Chem. 280: 23829-23836 [Abstract] [Full Text]
Yoon, Y. (2005). Regulation of Mitochondrial Dynamics: Another Process Modulated by Ca2+ Signals?. Sci Signal 2005: pe18-pe18 [Abstract] [Full Text]
Sugioka, R., Shimizu, S., Tsujimoto, Y. (2004). Fzo1, a Protein Involved in Mitochondrial Fusion, Inhibits Apoptosis. J. Biol. Chem. 279: 52726-52734 [Abstract] [Full Text]
Fannjiang, Y., Cheng, W.-C., Lee, S. J., Qi, B., Pevsner, J., McCaffery, J. M., Hill, R. B., Basanez, G., Hardwick, J. M. (2004). Mitochondrial fission proteins regulate programmed cell death in yeast. Genes Dev. 18: 2785-2797 [Abstract] [Full Text]
Lee, Y.-j., Jeong, S.-Y., Karbowski, M., Smith, C. L., Youle, R. J. (2004). Roles of the Mammalian Mitochondrial Fission and Fusion Mediators Fis1, Drp1, and Opa1 in Apoptosis. Mol. Biol. Cell 15: 5001-5011 [Abstract] [Full Text]
Brookes, P. S., Yoon, Y., Robotham, J. L., Anders, M. W., Sheu, S.-S. (2004). Calcium, ATP, and ROS: a mitochondrial love-hate triangle. Am. J. Physiol. Cell Physiol. 287: C817-C833 [Abstract] [Full Text]
Karbowski, M., Jeong, S.-Y., Youle, R. J. (2004). Endophilin B1 is required for the maintenance of mitochondrial morphology. JCB 166: 1027-1039 [Abstract] [Full Text]
Meeusen, S., McCaffery, J. M., Nunnari, J. (2004). Mitochondrial Fusion Intermediates Revealed in Vitro. Science 305: 1747-1752 [Abstract] [Full Text]
Mukamel, Z., Kimchi, A. (2004). Death-associated Protein 3 Localizes to the Mitochondria and Is Involved in the Process of Mitochondrial Fragmentation during Cell Death. J. Biol. Chem. 279: 36732-36738 [Abstract] [Full Text]
Tondera, D., Santel, A., Schwarzer, R., Dames, S., Giese, K., Klippel, A., Kaufmann, J. (2004). Knockdown of MTP18, a Novel Phosphatidylinositol 3-Kinase-dependent Protein, Affects Mitochondrial Morphology and Induces Apoptosis. J. Biol. Chem. 279: 31544-31555 [Abstract] [Full Text]
Terrones, O., Antonsson, B., Yamaguchi, H., Wang, H.-G., Liu, J., Lee, R. M., Herrmann, A., Basanez, G. (2004). Lipidic Pore Formation by the Concerted Action of Proapoptotic BAX and tBID. J. Biol. Chem. 279: 30081-30091 [Abstract] [Full Text]
Schinzel, A., Kaufmann, T., Schuler, M., Martinalbo, J., Grubb, D., Borner, C. (2004). Conformational control of Bax localization and apoptotic activity by Pro168. JCB 164: 1021-1032 [Abstract] [Full Text]
Stojanovski, D., Koutsopoulos, O. S., Okamoto, K., Ryan, M. T. (2004). Levels of human Fis1 at the mitochondrial outer membrane regulate mitochondrial morphology. J. Cell Sci. 117: 1201-1210 [Abstract] [Full Text]
Buccellato, L. J., Tso, M., Akinci, O. I., Chandel, N. S., Budinger, G. R. S. (2004). Reactive Oxygen Species Are Required for Hyperoxia-induced Bax Activation and Cell Death in Alveolar Epithelial Cells. J. Biol. Chem. 279: 6753-6760 [Abstract] [Full Text]
Karbowski, M., Arnoult, D., Chen, H., Chan, D. C., Smith, C. L., Youle, R. J. (2004). Quantitation of mitochondrial dynamics by photolabeling of individual organelles shows that mitochondrial fusion is blocked during the Bax activation phase of apoptosis. JCB 164: 493-499 [Abstract] [Full Text]
Yu, L.-Y., Jokitalo, E., Sun, Y.-F., Mehlen, P., Lindholm, D., Saarma, M., Arumae, U. (2003). GDNF-deprived sympathetic neurons die via a novel nonmitochondrial pathway. JCB 163: 987-997 [Abstract] [Full Text]
Yethon, J. A., Epand, R. F., Leber, B., Epand, R. M., Andrews, D. W. (2003). Interaction with a Membrane Surface Triggers a Reversible Conformational Change in Bax Normally Associated with Induction of Apoptosis. J. Biol. Chem. 278: 48935-48941 [Abstract] [Full Text]
Willis, S., Day, C. L., Hinds, M. G., Huang, D. C.S. (2003). The Bcl-2-regulated apoptotic pathway. J. Cell Sci. 116: 4053-4056 [Full Text]
James, D. I., Parone, P. A., Mattenberger, Y., Martinou, J.-C. (2003). hFis1, a Novel Component of the Mammalian Mitochondrial Fission Machinery. J. Biol. Chem. 278: 36373-36379 [Abstract] [Full Text]
Valentijn, A. J., Metcalfe, A. D., Kott, J., Streuli, C. H., Gilmore, A. P. (2003). Spatial and temporal changes in Bax subcellular localization during anoikis. JCB 162: 599-612 [Abstract] [Full Text]
Santel, A., Frank, S., Gaume, B., Herrler, M., Youle, R. J., Fuller, M. T. (2003). Mitofusin-1 protein is a generally expressed mediator of mitochondrial fusion in mammalian cells. J. Cell Sci. 116: 2763-2774 [Abstract] [Full Text]