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Mitochondrial Fusion Protects against Neurodegeneration in the Cerebellum

Chen, Hsiuchen and McCaffery, J. Michael and Chan, David C. (2007) Mitochondrial Fusion Protects against Neurodegeneration in the Cerebellum. Cell, 130 (3). pp. 548-562. ISSN 0092-8674. doi:10.1016/j.cell.2007.06.026.

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Mutations in the mitochondrial fusion gene Mfn2 cause the human neurodegenerative disease Charcot-Marie-Tooth type 2A. However, the cellular basis underlying this relationship is poorly understood. By removing Mfn2 from the cerebellum, we established a model for neurodegeneration caused by loss of mitochondrial fusion. During development and after maturity, Purkinje cells require Mfn2 but not Mfn1 for dendritic outgrowth, spine formation, and cell survival. In vivo, cell culture, and electron microscopy studies indicate that mutant Purkinje cells have aberrant mitochondrial distribution, ultrastructure, and electron transport chain activity. In fibroblasts lacking mitochondrial fusion, the majority of mitochondria lack mitochondrial DNA nucleoids. This deficiency provides a molecular mechanism for the dependence of respiratory activity on mitochondrial fusion. Our results show that exchange of mitochondrial contents is important for mitochondrial function as well as organelle distribution in neurons and have important implications for understanding the mechanisms of neurodegeneration due to perturbations in mitochondrial fusion.

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Chan, David C.0000-0002-0191-2154
Additional Information:© 2007 Elsevier Inc. Published: August 9, 2007. We are grateful to Dr. M. E. Hatten for invaluable discussions about cerebellar development and Dr. T. Tomoda for helpful advice in experimental techniques. We thank Drs. S. Dymecki, H. Westphal, P. Soriano, A. McMahon, A. Joyner, and W. Wisden for their generous sharing of mouse strains. We thank S. Detmer for reviewing the manuscript. We appreciate D. Solis for her care of and keen observation of our animals. This work was supported by NIH grant GM062967 and the United Mitochondrial Disease Foundation.
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United Mitochondrial Disease FoundationUNSPECIFIED
Issue or Number:3
Record Number:CaltechAUTHORS:20170707-132224024
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Official Citation:Hsiuchen Chen, J. Michael McCaffery, David C. Chan, Mitochondrial Fusion Protects against Neurodegeneration in the Cerebellum, Cell, Volume 130, Issue 3, 10 August 2007, Pages 548-562, ISSN 0092-8674, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:78862
Deposited By: Ruth Sustaita
Deposited On:10 Jul 2017 17:34
Last Modified:15 Nov 2021 17:43

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