CMT 2A: Mitochondrial dynamics-fusion, fission, movement, and mitophagy-in neur

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Hum Mol Genet. 2009 Oct 15;18(R2):R169-76.

Mitochondrial dynamics-fusion, fission, movement, and mitophagy-in

neurodegenerative diseases.

Chen H, Chan DC.

Division of Biology and Medical Institute, California Institute of

Technology, Pasadena, CA 91125, USA.

Neurons are metabolically active cells with high energy demands at locations

distant from the cell body. As a result, these cells are particularly dependent

on mitochondrial function, as reflected by the observation that diseases of

mitochondrial dysfunction often have a neurodegenerative component.

Recent discoveries have highlighted that neurons are reliant particularly on the

dynamic properties of mitochondria.

Mitochondria are dynamic organelles by several criteria. They engage in repeated

cycles of fusion and fission, which serve to intermix the lipids and contents of

a population of mitochondria. In addition, mitochondria are actively recruited

to subcellular sites, such as the axonal and dendritic processes of neurons.

Finally, the quality of a mitochondrial population is maintained through

mitophagy, a form of autophagy in which defective mitochondria are selectively

degraded. We review the general features of mitochondrial dynamics,

incorporating recent findings on mitochondrial fusion, fission, transport and

mitophagy.

Defects in these key features are associated with neurodegenerative disease.

Charcot-Marie-Tooth type 2A, a peripheral neuropathy, and dominant optic

atrophy, an inherited optic neuropathy, result from a primary deficiency of

mitochondrial fusion. Moreover, several major neurodegenerative

diseases--including Parkinson's, Alzheimer's and Huntington's disease--involve

disruption of mitochondrial dynamics.

Remarkably, in several disease models, the manipulation of mitochondrial fusion

or fission can partially rescue disease phenotypes. We review how mitochondrial

dynamics is altered in these neurodegenerative diseases and discuss the

reciprocal interactions between mitochondrial fusion, fission, transport and

mitophagy.