The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Activated Mitofusin 2 Signals Mitochondrial Fusion, Interferes with Bax Activation, and Reduces Susceptibility to Radical Induced Depolarization
Open accessAbstract
Mitochondrial fusion in higher eukaryotes requires at least two essential GTPases, Mitofusin 1 and Mitofusin 2 (Mfn2). We have created an activated mutant of Mfn2, which shows increased rates of nucleotide exchange and decreased rates of hydrolysis relative to wild type Mfn2. Mitochondrial fusion is stimulated dramatically within heterokaryons expressing this mutant, demonstrating that hydrolysis is not requisite for the fusion event, and supporting a role for Mfn2 as a signaling GTPase. Although steady-state mitochondrial fusion required the conserved intermembrane space tryptophan residue, this requirement was overcome within the context of the hydrolysis-deficient mutant. Furthermore, the punctate localization of Mfn2 is lost in the dominant active mutants, indicating that these sites are functionally controlled by changes in the nucleotide state of Mfn2. Upon staurosporine-stimulated cell death, activated Bax is recruited to the Mfn2-containing puncta; however, Bax activation and cytochrome c release are inhibited in the presence of the dominant active mutants of Mfn2. The dominant active form of Mfn2 also protected the mitochondria against free radical-induced permeability transition. In contrast to staurosporine-induced outer membrane permeability transition, pore opening induced through the introduction of free radicals was dependent upon the conserved intermembrane space residue. This is the first evidence that Mfn2 is a signaling GTPase regulating mitochondrial fusion and that the nucleotide-dependent activation of Mfn2 concomitantly protects the organelle from permeability transition. The data provide new insights into the critical relationship between mitochondrial membrane dynamics and programmed cell death.
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Cites
Proapoptotic BAX and BAK: A Requisite Gateway to Mitochondrial Dysfunction and Death
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Dynamin-related Protein Drp1 Is Required for Mitochondrial Division in Mammalian Cells
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The Role of Dynamin-Related Protein 1, a Mediator of Mitochondrial Fission, in Apoptosis
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Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A
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OPA1 requires mitofusin 1 to promote mitochondrial fusion
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Cited by
Mitochondrial membrane permeabilization in cell death
Kroemer, G., Galluzzi, L., & Brenner, C. (2007) · Physiological Reviews · doi:10.1152/physrev.00013.2006 · Cited by 3,598
Mitochondria: More Than Just a Powerhouse
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Self-citationOPA1 Controls Apoptotic Cristae Remodeling Independently from Mitochondrial Fusion
Frezza, C., Cipolat, S., Martins de Brito, O., Micaroni, M., Beznoussenko, G. V., Rudka, T., Bartoli, D., Polishuck, R. S., Danial, N. N., De Strooper, B., et al. (2006) · Cell · doi:10.1016/j.cell.2006.06.025 · Cited by 1,673
Mitochondrial dynamics and apoptosis
Suen, D.-F., Norris, K. L., & Youle, R. J. (2008) · Genes & Development · doi:10.1101/gad.1658508 · Cited by 1,270
Cassidy-Stone, A., Chipuk, J. E., Ingerman, E., Song, C., Yoo, C., Kuwana, T., Kurth, M. J., Shaw, J. T., Hinshaw, J. E., Green, D. R., et al. (2008) · Developmental Cell · doi:10.1016/j.devcel.2007.11.019 · Cited by 1,200
Metadata
- Authors
- Neuspiel, M., Zunino, R., Gangaraju, S., Rippstein, P., & McBride, H.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-07
- Volume
- 280
- Issue
- 26
- Pages
- 25060-25070
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1972044649
- Cited by
- 306
- References
- 54
- FWCI
- 6.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- 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. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m501599200
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