Defective Movement Of Cell's Power Plants Implicated In Commom Inherited Neurolo

[Guest guest]

Defective Movement Of Cell's Power Plants Implicated In Commom

Inherited Neurological Disorder

http://www.sciencedaily.com/releases/2007/01/070116205019.htm

Science Daily — Contrary to previous thinking, the inefficient

movement of cell's " power plants " --- the mitochondria --- within a

cell, rather than their low energy production, may be a contributing

factor in the development of Charcot-Marie-Tooth disease (CMT), new

research shows.

The study, published in the January 10 issue of The Journal of

Neuroscience, is the first to show that mutations in the gene

Mitofusin 2 (MFN2), known to cause a form of CMT, also disrupt the

movement of the cell's mitochondria, which deliver energy within the

cell. A minor disruption in mitochondria movement reduces the energy

supply, weakening or even killing the cell.

In CMT, which affects 1 in 2,500 individuals, nerves and muscles in

the feet and hands weaken, causing numbness and, in many cases, the

loss of function. CMT affects peripheral nerves, among the longest

nerves in the body where energy transport is vital.

" This work is of critical importance because the design of effective

therapeutic approaches requires an understanding of the underlying

disease mechanism, " says Popko, PhD, professor in neurological

diseases at the University of Chicago who is not connected to the

study.

The new research also provides strong evidence that effective energy

transportation is key to long cell life, according to senior author

H. Baloh, PhD, at the Washington University School of

Medicine.

Using rat tissue, Baloh and colleagues removed neurons similar to

those affected in CMT patients. They then inserted mutant MFN2 genes

in the nucleus of those cells using engineered viruses. Time-lapse

videos were taken with a fluorescent microscope in order to observe

the speed at which the mitochondria moved. In normal cells,

mitochondria are highly mobile. However, in the neurons with mutant

MFN2 genes, movement is significantly reduced.

Still unknown is exactly how the mutated MFN2 protein alters

mitochondrial transport. Piecing together this puzzle not only could

lead to an enhanced understanding of how this phenomenon occurs, but

may also reveal how to prevent or counteract it. The researchers

also believe that there may be an additional and as yet undetected

role of MFN2 in attaching mitochondria to motor proteins that aid

movement.

The study was supported by a grant from the Muscular Dystrophy

Association.

The Journal of Neuroscience is published by the Society for

Neuroscience, an organization of more than 36,500 basic scientists

and clinicians who study the brain and nervous system.

Note: This story has been adapted from a news release issued by

Society for Neuroscience.