Mitochondrial fusion
Mitochondria are dynamic organelles with the ability to fuse and divide (fission), forming constantly changing tubular networks in most eukaryotic cells.
When cells experience metabolic or environmental stresses, mitochondrial fusion and fission work to maintain functional mitochondria.
[3] The components of this process can influence programmed cell death and lead to neurodegenerative disorders such as Parkinson's disease.
Specifically, fusion assists in modifying stress by integrating the contents of slightly damaged mitochondria as a form of complementation.
By enabling genetic complementation, fusion of the mitochondria allows for two mitochondrial genomes with different defects within the same organelle to individually encode what the other lacks.
These two proteins are mitofusin contained within humans that can alter the morphology of affected mitochondria in over-expressed conditions.
In Drosophila, Fzo is found in postmeiotic spermatids and the dysfunction of this protein results in male sterility.
However, a deletion of Fzo1 in budding yeast results in smaller, spherical mitochondria due to the lack of mitochondrial DNA (mtDNA).
These resulting changes indicate that inner mitochondrial membrane structure is linked with regulatory pathways in influencing cell life and death.
It has been suggested that the type of cell determines the method of action but it has yet to be concluded whether or not Mfn1 and Mfn2 perform the same function in the process or if they are separate.
Mouse embryo fibroblasts (MEFs) originated from the double knock-out mice, which do survive in culture even though there is a complete absence of fusion, but parts of their mitochondria show a reduced mitochondrial DNA (mtDNA) copy number and lose membrane potential.
Chen and Chan (2010) have discussed the molecular basis of mitochondrial fusion, its protective role in neurodegeneration, and its importance in cellular function.
Cells with reduced mitochondrial fusion show a subpopulation of mitochondria that lack mtDNA nucleoids.
For instance, the formation of tethered structures in vitro occurs more readily when mitochondria are isolated from cells overexpressing Mfn1 than Mfn2.
[9] In addition, Mfn2 specifically has been shown to associate with Bax and Bak (Bcl-2 family, TC#1.A.21), resulting in altered Mfn2 activity, indicating that the mitofusins possess unique functional characteristics.
This suggests that control of the expression levels of each protein likely represents the most basic form of regulation to alter mitochondrial dynamics in mammalian tissues.
Hoppins et al., 2009 showed that Ugo1 is a modified member of this family, containing three transmembrane domains and existing as a dimer, a structure that is critical for the fusion function of Ugo1.
