Mitochondrial fission factor explained

Mitochondrial fission factor (Mff) is a protein that in humans is encoded by the MFF gene.^[1] Its primary role is in controlling the division of mitochondria. Mitochondrial morphology changes by continuous fission in order to create interconnected network of mitochondria. This activity is crucial for normal function of mitochondria.^[2] Mff is anchored to the mitochondrial outer membrane through the C-terminal transmembrane domain, extruding the bulk of the N-terminal portion containing two short amino acid repeats in the N-terminal half and a coiled-coil domain just upstream of the transmembrane domain into the cytosol.^[3] It has also been shown to regulate peroxisome morphology.^[4]

Role in mitochondrial fission

See main article: mitochondrial fission.

Mff is an outer mitochondrial membrane protein that binds to the GTPase Drp1; the Mff-Drp1 complex is what promotes mitochondrial fission. Knockdown of Mff causes the mitochondrial network to expand (by releasing the Drp1 foci from the outer mitochondrial membrane), while Mff overexpression causes it to become fragmented (by stimulating mitochondrial recruitment of Drp1).^[5] DRP1 is mainly cytosolic, but translocate to the mitochondrial surface in order to mediate fission of mitochondria. Mitochondrial fission factor plays a crucial role in engaging Drp1 to the outer mitochondrial membrane in order to direct mitochondrial fission.^[2] Mff overexpression leads to various defective conditions in humans such as neurogenerative disorders like Huntington’s disease, Alzheimer’s disease, metabolic disorders, cardiovascular disease and majorly cancer. re-fusing mitochondria may be a viable therapeutic strategy in diseases with excessive mitochondrial fission.^[6]

Further reading

• Igci YZ, Arslan A, Akarsu E, Erkilic S, Igci M, Oztuzcu S, Cengiz B, Gogebakan B, Cakmak EA, Demiryurek AT . 6 . Differential expression of a set of genes in follicular and classic variants of papillary thyroid carcinoma . Endocrine Pathology . 22 . 2 . 86–96 . June 2011 . 21509594 . 10.1007/s12022-011-9157-8 . 11869197 .

Notes and References

1. Web site: Entrez Gene: mitochondrial fission factor.
2. Otera H, Wang C, Cleland MM, Setoguchi K, Yokota S, Youle RJ, Mihara K . Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells . The Journal of Cell Biology . 191 . 6 . 1141–1158 . December 2010 . 21149567 . 10.1083/jcb.201007152 . 3002033 .
3. Otera . Hidenori . Wang . Chunxin . Cleland . Megan M. . Setoguchi . Kiyoko . Yokota . Sadaki . Youle . Richard J. . Mihara . Katsuyoshi . 2010-12-13 . Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells . Journal of Cell Biology . 191 . 6 . 1141–1158 . 10.1083/jcb.201007152 . 1540-8140. free . 21149567 . 3002033 .
4. Gandre-Babbe S, van der Bliek AM . The novel tail-anchored membrane protein Mff controls mitochondrial and peroxisomal fission in mammalian cells . Molecular Biology of the Cell . 19 . 6 . 2402–2412 . June 2008 . 18353969 . 2397315 . 10.1091/mbc.E07-12-1287 .
5. Otera H, Wang C, Cleland MM, Setoguchi K, Yokota S, Youle RJ, Mihara K . Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells . The Journal of Cell Biology . 191 . 6 . 1141–1158 . December 2010 . 21149567 . 3002033 . 10.1083/jcb.201007152 .
6. Chen . Le . Winger . Allison J. . Knowlton . Anne A. . 2014-08-08 . Mitochondrial dynamic changes in health and genetic diseases . Molecular Biology Reports . 41 . 11 . 7053–7062 . 10.1007/s11033-014-3663-y . 25103020 . 0301-4851. 5683169 .