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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 initial stages of apoptosis, which subsequently become mitochondrial scission sites. A dominant negative mutant of Drp1, Drp1^K38A, inhibits apoptotic scission of mitochondria, but does not inhibit Bax translocation or coalescence into foci. However, Drp1^K38A causes the accumulation of mitochondrial fission intermediates that are associated with clusters of Bax. Surprisingly, Drp1 and Mfn2, but not other proteins implicated in the regulation of mitochondrial morphology, colocalize with Bax in these foci. We suggest that Bax participates in apoptotic fragmentation of mitochondria.

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• 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]  
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• Meeusen, S., McCaffery, J. M., Nunnari, J. (2004). Mitochondrial Fusion Intermediates Revealed in Vitro. Science 305: 1747-1752 [Abstract] [Full Text]  
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• 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]  
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• Schinzel, A., Kaufmann, T., Schuler, M., Martinalbo, J., Grubb, D., Borner, C. (2004). Conformational control of Bax localization and apoptotic activity by Pro168. J. Cell Biol. 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. J. Cell Biol. 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. J. Cell Biol. 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. J. Cell Biol. 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]  

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