Cellular and Molecular Life Sciences

, Volume 67, Issue 20, pp 3435–3447 | Cite as

Mitochondrial dynamics in cell death and neurodegeneration

  • Dong-Hyung Cho
  • Tomohiro Nakamura
  • Stuart A. Lipton
Review

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.

Keywords

Mitochondria dynamics Neurodegenerative diseases Drp1 Opa1 Mitofusin 1/2 Cell death 

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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Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  • Dong-Hyung Cho
    • 1
    • 2
    • 3
  • Tomohiro Nakamura
    • 1
  • Stuart A. Lipton
    • 1
  1. 1.Center for Neuroscience, Aging, and Stem Cell ResearchSanford-Burnham Medical Research InstituteLa JollaUSA
  2. 2.Institute for Innovative Cancer Research, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  3. 3.Graduate School of East-West Medical ScienceKyung Hee UniversityYonginKorea

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