Mitofusin 1: can be used in the repair of damaged mitochondrial DNA. Mitochondria produce cellular energy that begins to run low with age. In the future it may become important to correct dysfunctional and aberrant mitochondrial DNA to solve certain diseases and restore cellular energy levels.

Defects in mitochondria are thought to underlie a variety of degenerative disorders in humans. Myopathies, neuropathies, encephalomyopathies and many other diseases have been associated with mutations in the mitochondrial DNA (mtDNA). In many of these diseases onset of clinical symptoms is late, occurring as the ratio of mutant to wild-type mtDNA passes a critical threshold depending on energy demands of the particular tissue. Recent studies of the effect of mtDNA mutations on disease phenotypes in a transgenic mouse model suggested an important protection mechanism against the onset of disease symptoms. In individual cells containing both wild-type and mutant mitochondria, immunoelectron microscopy revealed that most if not all of the mitochondria showed cytochrome c oxidase activity.

This observation of complementation of mtDNA mutations in mice suggested that fusion between mitochondria with different genotypes may provide an important mechanism for protecting cells and tissues from expressing disease phenotypes caused by mitochondrial dysfunction based on mutations in the mtDNA. In addition, recent observations have suggested inter-mitochondrial complementation in cell culture. Although these findings are still controversial, they have focused attention on molecular mechanisms that might mediate and regulate mitochondrial fusion in mammalian cells.

Mitofusin proteins, Mfn1 and Mfn2, belong to the family of high-molecular mass transmembrane GTPases, which have homologues in organisms from yeast to humans. They are localized in the outer mitochondrial membrane and have large N-terminal and relatively short C-terminal domains exposed towards the cytoplasm. They have a GTPase domain near the N-terminus, a coiled-coil domain, two transmembrane spanning domains, and a coiled-coil domain facing the cytoplasm in the C-terminal tail. Human Mfn2 (757 amino acid residues) is 62% identical and 77% similar to human Mfn1 (741 amino acid residues). The relative mRNA or protein expression levels of Mfn1 and Mfn2 vary between tissues: Mfn1 predominates in heart, liver, pancreas, adrenal glands and testis, whereas Mfn2 is more abundant in heart, skeletal muscle, brain, adrenal glands and brown adipose tissue. Several cell types, for example, mouse embryo fibroblasts and HeLa cells, express both Mfn1 and Mfn2. The co-existence of two isoforms of Mfn in mammalian cells raises the question as to whether they play similar, separate or dependent biological roles.

Mitochondria are highly dynamic organelles exhibiting an elaborate morphology and fine structure. Fusion and fission processes contribute to the maintenance and dynamics of mitochondrial morphology. The Mitofusins are essential for the controlled fusion of mitochondrial membranes. Recent reports shed new light on the physiological importance of Mitofusin function suggesting a role in mitochondrial metabolism, apoptosis as well as cellular signaling.