The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Altered Axonal Mitochondrial Transport in the Pathogenesis of Charcot-Marie-Tooth Disease from Mitofusin 2 Mutations
Open accessAbstract
Mutations in the mitochondrial fusion protein mitofusin 2 (MFN2) are the most commonly identified cause of Charcot-Marie-Tooth type 2 (CMT2), a dominantly inherited disease characterized by degeneration of peripheral sensory and motor axons. However, the mechanism by which mutations in this ubiquitously expressed mitochondrial fusion protein lead to neuropathy has not yet been elucidated. To explore how MFN2 mutations lead to degeneration of peripheral axons, we expressed neuropathy-associated forms of MFN2 in cultured dorsal root ganglion neurons, cells preferentially affected in CMT2. Disease-associated MFN2 mutant proteins induced abnormal clustering of small fragmented mitochondria in both neuronal cell bodies and proximal axons. Interestingly, transport of mitochondria in axons was significantly impaired in neurons expressing disease-mutated forms of MFN2. The diminished axonal mitochondrial transport was not attributable to diminished ATP levels in the neurons, and oxidative respiration was normal in mutant MFN2-expressing cells. Additionally, mitochondrial oxidative enzyme activity was normal in muscle mitochondria from a CMT2 patient with an MFN2 mutation, further supporting that abnormal mitochondrial transport in neurons is independent from an energy production defect. This abnormal mitochondrial trafficking provides a likely explanation for the selective susceptibility of the longest peripheral axons to MFN2 mutations, in which proper localization of mitochondria is critical for axonal and synaptic function.
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Cites
Chen, H., Detmer, S. A., Ewald, A. J., Griffin, E. E., Fraser, S. E., & Chan, D. C. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200211046 · Cited by 2,601
Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A
Züchner, S., Mersiyanova, I. V., Muglia, M., Bissar-Tadmouri, N., Rochelle, J., Dadali, E. L., Zappia, M., Nelis, E., Patitucci, A., Senderek, J., et al. (2004) · Nature Genetics · doi:10.1038/ng1341 · Cited by 1,572
Disruption of Fusion Results in Mitochondrial Heterogeneity and Dysfunction
Chen, H., Chomyn, A., & Chan, D. C. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m503062200 · Cited by 1,376 · cited 1×
“Oxidative respiration studies were performed using a Clark oxygen electrode (Oxygraph; Hansatech Instruments, Norfolk, UK) similar to that described previously (Chen et al., 2005).”
MethodOPA1 requires mitofusin 1 to promote mitochondrial fusion
Cipolat, S., de Brito, O. M., Dal Zilio, B., & Scorrano, L. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407043101 · Cited by 1,300
Increased Nuclear NAD Biosynthesis and SIRT1 Activation Prevent Axonal Degeneration
Araki, T., Sasaki, Y., & Milbrandt, J. (2004) · Science · doi:10.1126/science.1098014 · Cited by 1,060
Self-citationControl of mitochondrial morphology by a human mitofusin
Santel, A., & Fuller, M. T. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.5.867 · Cited by 1,012
Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity
Ishihara, N., Eura, Y., & Mihara, K. (2004) · Journal of Cell Science · doi:10.1242/jcs.01565 · Cited by 731 · cited 1×
“This stems from the concept that MFN2 may function as a regulatory GTPase, based on its high GTP affinity and low GTP hydrolysis rate (Ishihara et al., 2004; Zorzano and Pich, 2006).”
BackgroundTanaka, Y., Kanai, Y., Okada, Y., Nonaka, S., Takeda, S., Harada, A., & Hirokawa, N. (1998) · Cell · doi:10.1016/s0092-8674(00)81459-2 · Cited by 654
Pich, S., Bach, D., Briones, P., Liesa, M., Camps, M., Testar, X., Palacín, M., & Zorzano, A. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi149 · Cited by 455
Karbowski, M., Arnoult, D., Chen, H., Chan, D. C., Smith, C. L., & Youle, R. J. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200309082 · Cited by 433
Cited by
Mitochondria: In Sickness and in Health
Nunnari, J., & Suomalainen, A. (2012) · Cell · doi:10.1016/j.cell.2012.02.035 · Cited by 3,479
Mitochondrial form and function
Friedman, J. R., & Nunnari, J. (2014) · Nature · doi:10.1038/nature12985 · Cited by 1,803
Functions and dysfunctions of mitochondrial dynamics
Detmer, S. A., & Chan, D. C. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2275 · Cited by 1,369
PINK1-Phosphorylated Mitofusin 2 Is a Parkin Receptor for Culling Damaged Mitochondria
Chen, Y., & Dorn, G. W. (2013) · Science · doi:10.1126/science.1231031 · Cited by 1,323
Mitochondrial fragmentation in neurodegeneration.
Knott, A. B., Perkins, G., Schwarzenbacher, R., & Bossy-Wetzel, E. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2417 · Cited by 1,002
Mitochondrial Dynamics in Mammalian Health and Disease
Liesa, M., Palacín, M., & Zorzano, A. (2009) · Physiological Reviews · doi:10.1152/physrev.00030.2008 · Cited by 953
Mitochondrial fusion protects against neurodegeneration in the cerebellum
Chen, H., McCaffery, J. M., & Chan, D. C. (2007) · Cell · doi:10.1016/j.cell.2007.06.026 · Cited by 924
Axonal transport deficits and neurodegenerative diseases
Millecamps, S., & Julien, J.-P. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3380 · Cited by 755
Mitochondria: The Next (Neurode)Generation
Schon, E. A., & Przedborski, S. (2011) · Neuron · doi:10.1016/j.neuron.2011.06.003 · Cited by 568
Palmer, C. S., Elgass, K. D., Parton, R. G., Osellame, L. D., Stojanovski, D., & Ryan, M. T. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.479873 · Cited by 301
Amyloid‐Beta Interaction with Mitochondria
Pagani, L., & Eckert, A. (2011) · International Journal of Alzheimer’s Disease · doi:10.4061/2011/925050 · Cited by 309
Boldogh, I. R., & Pon, L. A. (2007) · Trends in Cell Biology · doi:10.1016/j.tcb.2007.07.008 · Cited by 270
Nmnat delays axonal degeneration caused by mitochondrial and oxidative stress
Press, C., & Milbrandt, J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.0525-08.2008 · Cited by 137
“It results in a host of cellular abnormalities, including decreased ATP synthesis, disrupted mitochondrial fusion and transport, and the increased generation of reactive oxygen species (ROS) (Lin and Beal, 2006; Baloh et al., 2007).”
BackgroundSelf-citationDysregulated mitophagy and mitochondrial organization in optic atrophy due to OPA1 mutations
Liao, C., Ashley, N., Diot, A., Morten, K., Phadwal, K., Williams, A., Fearnley, I., Rosser, L., Lowndes, J., Fratter, C., et al. (2017) · Neurology · doi:10.1212/wnl.0000000000003491 · Cited by 97
Trevisan, T., Pendin, D., Montagna, A., Bova, S., Ghelli, A. M., & Daga, A. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.04.017 · Cited by 86
Chowdhury, S. K. R., Dobrowsky, R. T., & Fernyhough, P. (2011) · Mitochondrion · doi:10.1016/j.mito.2011.06.007 · Cited by 82
van Hameren, G., Campbell, G., Deck, M., Berthelot, J., Gautier, B., Quintana, P., Chrast, R., & Tricaud, N. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0740-4 · Cited by 83
Mitofusin 2-Deficiency Suppresses Cell Proliferation through Disturbance of Autophagy
Ding, Y., Gao, H., Zhao, L., Wang, X., & Zheng, M. (2015) · PLOS ONE · doi:10.1371/journal.pone.0121328 · Cited by 59
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Guardia-Laguarta, C., Area-Gomez, E., Schon, E. A., & Przedborski, S. (2015) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2015.00017 · Cited by 44
The Pathophysiology of Axonal Transport in Alzheimer's Disease
Vicario-Orri, E., Opazo, C. M., & Muñoz, F. J. (2014) · Journal of Alzheimer’s Disease · doi:10.3233/jad-141080 · Cited by 41
Hannan, S. B., Dräger, N. M., Rasse, T. M., Voigt, A., & Jahn, T. R. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13532 · Cited by 38
Iuzzolino, A., Pellegrini, F. R., Rotili, D., Degrassi, F., & Trisciuoglio, D. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05227-x · Cited by 33
The ER ladder is a unique morphological feature of developing mammalian axons
Zamponi, E., Meehl, J. B., & Voeltz, G. K. (2022) · Developmental Cell · doi:10.1016/j.devcel.2022.05.002 · Cited by 32
Metadata
- Authors
- Baloh, R. H., Schmidt, R. E., Pestronk, A., & Milbrandt, J.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-01-10
- Volume
- 27
- Issue
- 2
- Pages
- 422-430
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W2039409049
- Cited by
- 451
- References
- 12
- FWCI
- 11.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
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