MFN2

Mitofusin-2 is a is_associated_with::protein that in humans is encoded by the MFN2 is_associated_with::gene. Mitofusins are is_associated_with::GTPases embedded in the outer membrane of the mitochondria. In mammals is_associated_with::MFN1 and MFN2 are essential for is_associated_with::mitochondrial fusion.

Function
Mitofusin-2 is a mitochondrial membrane protein that participates in is_associated_with::mitochondrial fusion and contributes to the maintenance and operation of the mitochondrial network. Mitochondria function as a dynamic network constantly undergoing fusion and fission. The balance between fusion and fission is important in maintaining the integrity of the mitochondria and facilitates the mixing of the membranes and the exchange of DNA between mitochondria. MFN1 and MFN2 mediate outer membrane fusion while is_associated_with::OPA1 is involved in inner membrane fusion.

Mitochondrial fusion is essential for embryonic development. knockout mice for either MFN1 or MFN2 have fusion deficits and die midgestation. MFN2 knockout mice die at embryonic day 11.5 due to a defect in the giant cell layer of the placenta.

Fusion is also important for mitochondrial transport and localization in neuronal processes. Conditional MFN2 knockout mice show degeneration in the is_associated_with::Purkinje cells of the cerebellum, as well as improperly localized mitochondria in the dendrites. MFN2 also associates with the MIRO-Milton complex which links the mitochondria to the is_associated_with::kinesin motor.

Clinical significance
Mutations of the gene are implicated in is_associated_with::Charcot-Marie-Tooth disease. Charcot-Marie-Tooth disease type 2A (CMT2A) is caused by mutations in the MFN2 gene. While the symptoms of CMT2A are variable they are characterized by a sometimes early onset, severe phenotype, and optic atrophy. Mutations in OPA1 also cause optic atrophy, which suggests a common role of is_associated_with::mitochondrial fusion in neuronal dysfunction. The exact mechanism of how mutations in MFN2 selectively cause the degeneration of long peripheral axons is not known. There is evidence suggesting that it could be due to defects in the axonal transport of mitochondria.

The MFN2 protein may play a role in the pathophysiology of obesity.

This protein is involved in the regulation of vascular smooth muscle cell proliferation.