CMT Disease-Causing Mutation Disrupts Movement of Cells Powerhouse

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New research shows how a mutation causes a common inherited neurodegenerative

disease, according to a study in the March 24 issue of The Journal of

Neuroscience. The study shows that the mutation of a specific protein known to

cause Charcot-Marie-Tooth disrupts the movement of mitochondria, the

energy-supplying machine inside each cell. The regulated movement of

mitochondria along nerve cell fibers is vital to normal communication between

the brain and muscles.

DISEASE-CAUSING MUTATION DISRUPTS MOVEMENT OF CELLS POWER HOUSE

Animal study furthers our understanding of inherited neurodegenerative disease

New research shows how a mutation causes a common inherited neurodegenerative

disease, according to a study in the March 24 issue of The Journal of

Neuroscience. The study shows that the mutation of a specific protein known to

cause Charcot-Marie-Tooth (CMT) disrupts the movement of mitochondria, the

energy-supplying machines inside each cell. The regulated movement of

mitochondria along nerve cell fibers is vital to normal communication between

the brain and muscles.

A mutation in the protein mitofusin 2 had been known to cause one type of CMT, a

common inherited neurological disorder characterized by a loss of muscle tissue

and sensation in the limbs, which affects about 2.6 million people. In this

study, a team of researchers lead by Baloh, MD, PhD, of Washington

University School of Medicine, examined the role of mitofusin proteins in the

cell to learn more precisely how the mutation causes the disease.

Our study provides the first evidence that mitofusins directly regulate the

movement of mitochondria in nerve fibers,¡¨ Baloh said. Furthermore, our work

suggests the basis for this particular form of CMT is the abnormal movement of

mitochondria in these fibers.¡¨

Mitochondria are dynamic cellular power providers that travel to places in the

cell where energy is needed. All this activity hinges on a series of molecular

signals that regulate where mitochondria go.

Baloh and his colleagues used images of live cells taken from mice to study the

movement of mitochondria, which moved slower in cells with mutated mitofusin 2,

suggesting that the protein directly affects their transport. Until now,

researchers had been unsure as to whether the abnormality lay in their transport

along, or attachment to, nerve fibers.

This discovery places this type of CMT in the ever-growing list of

neurodegenerative diseases caused by transport problems and strengthens the

possibility of using general enhancers of this process as therapy for different

types of diseases, said Timmerman, PhD, of the University of Antwerp in

Belgium, who was unaffiliated with the study.

The authors also suggest that a related protein called mitofusin 1 might someday

serve to compensate for a mutated and malfunctioning mitofusin 2. Although

mitofusins 1 and 2 are different proteins, they play similar roles in a cell.

Baloh and his team suggest that mitofusin 1 may be able to perform the function

of mitofusin 2 and regulate the transport of mitochondria. Finding a way to

increase the levels of mitofusin 1 might have therapeutic effects for patients

who have mutated mitofusin 2.