(mentions CMT) Mitochondrial dynamics in cell death and neurodegeneration

[Guest guest]

Mitochondrial dynamics in cell death and neurodegeneration.

Cho DH, Nakamura T, Lipton SA.

Center for Neuroscience, Aging, and Stem Cell Research, Sanford-Burnham Medical

Research Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA.

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 Abeta

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.