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Mitochondrial dynamics in cell death and neurodegeneration

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Abstract

Mitochondria are highly dynamic organelles that continuously undergo two opposite processes, fission and fusion. Mitochondrial dynamics influence not only mitochondrial morphology, but also mitochondrial biogenesis, mitochondrial distribution within the cell, cell bioenergetics, and cell injury or death. Drp1 mediates mitochondrial fission, whereas Mfn1/2 and Opa1 control mitochondrial fusion. Neurons require large amounts of energy to carry out their highly specialized functions. Thus, mitochondrial dysfunction is a prominent feature in a variety of neurodegenerative diseases. Mutations of Mfn2 and Opa1 lead to neuropathies such as Charcot-Marie-Tooth disease type 2A and autosomal dominant optic atrophy. Moreover, both Aβ peptide and mutant huntingtin protein induce mitochondrial fragmentation and neuronal cell death. In addition, mutants of Parkinson’s disease-related genes also show abnormal mitochondrial morphology. This review highlights our current understanding of abnormal mitochondrial dynamics relevant to neuronal synaptic loss and cell death in neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and Huntington’s disease.

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Abbreviations

Drp1:

dynamin-related protein 1

Opa1:

optic atrophy protein 1

Mfn1/2:

mitofusin1/2

AD:

Alzheimer’s disease

PD:

Parkinson’s disease

HD:

Huntinton’s disease

ADOA:

Autosomal dominant optic atrophy

CTM2A:

Charcot-Marie-Tooth neuropathy type 2A

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Acknowledgments

This study was supported in part by NIH grants P01 HD29587, P01 ES01673, R01 EY05477 and R01 EY09024 (to S.A.L.). Additional support was provided by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health, Welfare and Family Affairs, Republic of Korea (A090013 and A092042) (to D.-H.C.).

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  1. Center for Neuroscience, Aging, and Stem Cell Research, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Dong-Hyung Cho, Tomohiro Nakamura & Stuart A. Lipton

  2. Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Pungpap-dong, Songpa-gu, Seoul, 138-736, Korea

    Dong-Hyung Cho

  3. Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Gyeonggi, 446-701, Korea

    Dong-Hyung Cho

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  1. Dong-Hyung Cho
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  2. Tomohiro Nakamura
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Correspondence to Stuart A. Lipton.

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Cho, DH., Nakamura, T. & Lipton, S.A. Mitochondrial dynamics in cell death and neurodegeneration. Cell. Mol. Life Sci. 67, 3435–3447 (2010). https://doi.org/10.1007/s00018-010-0435-2

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  • DOI: https://doi.org/10.1007/s00018-010-0435-2

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