CMT 2: Mitochondrial Trafficking and Morphology in Neuronal Injury

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Biochim Biophys Acta. 2009 Sep 9.

Mitochondrial Trafficking and Morphology in Neuronal Injury.

Rintoul GL, Reynolds IJ.

Department of Biological Sciences, Simon Fraser University, Burnaby BC V5A 1S6,

Canada.

Alterations in mitochondrial function may have a central role in the

pathogenesis of many neurodegenerative diseases. The study of mitochondrial

dysfunction has typically focused on ATP generation, calcium homeostasis and the

production of reactive oxygen species. However, there is a growing appreciation

of the dynamic nature of mitochondria within cells.

Mitochondria are highly motile organelles, and also constantly undergo fission

and fusion. This raises the possibility that impairment of mitochondrial

dynamics could contribute to the pathogenesis of neuronal injury.

In this review we describe the mechanisms that govern mitochondrial movement,

fission and fusion. The key proteins that are involved in mitochondrial fission

and fusion have also been linked to some inherited neurological diseases,

including autosomal dominant optic atrophy and Charcot-Marie-Tooth disease 2A.

We will discuss the evidence that altered movement, fission and fusion are

associated with impaired neuronal viability.

There is a growing collection of literature that links impaired mitochondrial

dynamics to a number of disease models. Additionally, the concept that the

failure to deliver a functional mitochondrion to the appropriate site within a

neuron could contribute to neuronal dysfunction provides an attractive framework

for understanding the mechanisms underlying neurologic disease. However, it

remains difficult to clearly establish that altered mitochondrial dynamics

clearly represent a cause of neuronal dysfunction.