The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
Mitofusin 2 Is Necessary for Transport of Axonal Mitochondria and Interacts with the Miro/Milton Complex
Open accessAbstract
Mitofusins (Mfn1 and Mfn2) are outer mitochondrial membrane proteins involved in regulating mitochondrial dynamics. Mutations in Mfn2 cause Charcot-Marie-Tooth disease (CMT) type 2A, an inherited disease characterized by degeneration of long peripheral axons, but the nature of this tissue selectivity remains unknown. Here, we present evidence that Mfn2 is directly involved in and required for axonal mitochondrial transport, distinct from its role in mitochondrial fusion. Live imaging of neurons cultured from Mfn2 knock-out mice or neurons expressing Mfn2 disease mutants shows that axonal mitochondria spend more time paused and undergo slower anterograde and retrograde movements, indicating an alteration in attachment to microtubule-based transport systems. Furthermore, Mfn2 disruption altered mitochondrial movement selectively, leaving transport of other organelles intact. Importantly, both Mfn1 and Mfn2 interact with mammalian Miro (Miro1/Miro2) and Milton (OIP106/GRIF1) proteins, members of the molecular complex that links mitochondria to kinesin motors. Knockdown of Miro2 in cultured neurons produced transport deficits identical to loss of Mfn2, indicating that both proteins must be present at the outer membrane to mediate axonal mitochondrial transport. In contrast, disruption of mitochondrial fusion via knockdown of the inner mitochondrial membrane protein Opa1 had no effect on mitochondrial motility, indicating that loss of fusion does not inherently alter mitochondrial transport. These experiments identify a role for mitofusins in directly regulating mitochondrial transport and offer important insight into the cell type specificity and molecular mechanisms of axonal degeneration in CMT2A and dominant optic atrophy.
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Cites
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Mitofusin 2 tethers endoplasmic reticulum to mitochondria
de Brito, O. M., & Scorrano, L. (2008) · Nature · doi:10.1038/nature07534 · Cited by 2,442
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 · cited 4×
“CMT2A and dominant optic atrophy are associated with mutations in MFN2 and OPA1, respectively; both are ubiquitously expressed proteins essential for mitochondrial fusion (Alexander et al., 2000; Delettre et al., 2000; Zuchner et al., 2004).”
BackgroundInfluentialDisruption 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 5×
“Although the precise reason for mitochondrial fusion remains unclear, interruption of mitochondrial fusion (via loss of Opa1 or Mfn1/2) leads to loss of mitochondrial potential and diminished oxidative phosphorylation, indicating it is critical for maintaining mitochondrial function (Olichon et al., 2003; Chen et al.,…”
BackgroundInfluentialOPA1 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
Mitochondrial dynamics and apoptosis
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“Perhaps it should not be a surprise then that mitofusins have been reported to perform numerous functions, including the regulation of mitochondrial fusion (Chan, 2006), endoplasmic reticulum (ER)–mitochondrial tethering (de Brito and Scorrano, 2008), apoptotic cell death and outer membrane permeability (Suen et al.,…”
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Increased Nuclear NAD Biosynthesis and SIRT1 Activation Prevent Axonal Degeneration
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Self-citationMitochondrial fusion protects against neurodegeneration in the cerebellum
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Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity
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“The mitochondrial fusion apparatus consists primarily of mitofusin 1 and mitofusin 2 (Mfn1 and Mfn2) located on the OMM, and Opa1 located on the inner mitochondrial membrane (Rojo et al., 2002; Chen et al., 2003; Eura et al., 2003; Wong et al., 2003; Cipolat et al., 2004).”
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Drosophila Miro Is Required for Both Anterograde and Retrograde Axonal Mitochondrial Transport
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Hereditary optic neuropathies: from the mitochondria to the optic nerve.
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Mitochondrial form and function
Friedman, J. R., & Nunnari, J. (2014) · Nature · doi:10.1038/nature12985 · Cited by 1,803
Mitochondrial Dynamics and Its Involvement in Disease
Chan, D. C. (2020) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-012419-032711 · Cited by 1,416
Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: Recent advances.
Wang, W., Zhao, F., Ma, X., Perry, G., & Zhu, X. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00376-6 · Cited by 1,274
Mitochondrial dynamics and mitochondrial quality control
Ni, H.-M., Williams, J. A., & Ding, W.-X. (2015) · Redox Biology · doi:10.1016/j.redox.2014.11.006 · Cited by 931
Gegg, M. E., Cooper, J. M., Chau, K.-Y., Rojo, M., Schapira, A. H. V., & Taanman, J.-W. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq419 · Cited by 910
Metadata
- Authors
- Misko, A., Jiang, S., Wegorzewska, I., Milbrandt, J., & Baloh, R. H.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-03-24
- Volume
- 30
- Issue
- 12
- Pages
- 4232-4240
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W2168082049
- Cited by
- 641
- References
- 15
- FWCI
- 17.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
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