Mitochondrial fission factor (Mff) is a protein that in humans is encoded by the MFF gene.[5] 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.[6] 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.[7] It has also been shown to regulate peroxisome morphology.[8]
Role in mitochondrial fission
editMff 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).[9] DRP1 is mainly cytosolic, but translocate to the mitochondrial surface in order to mediate fission of mitochondria.[6] Mitochondrial fission factor plays a crucial role in engaging Drp1 to the outer mitochondrial membrane in order to direct mitochondrial fission.[6] 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.[10]
References
edit- ^ a b c GRCh38: Ensembl release 89: ENSG00000168958 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026150 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: mitochondrial fission factor".
- ^ a b c Otera H, Wang C, Cleland MM, Setoguchi K, Yokota S, Youle RJ, Mihara K (December 2010). "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. doi:10.1083/jcb.201007152. PMC 3002033. PMID 21149567.
- ^ Otera H, Wang C, Cleland MM, Setoguchi K, Yokota S, Youle RJ, Mihara K (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. doi:10.1083/jcb.201007152. ISSN 1540-8140. PMC 3002033. PMID 21149567.
- ^ Gandre-Babbe S, van der Bliek AM (June 2008). "The novel tail-anchored membrane protein Mff controls mitochondrial and peroxisomal fission in mammalian cells". Molecular Biology of the Cell. 19 (6): 2402–2412. doi:10.1091/mbc.E07-12-1287. PMC 2397315. PMID 18353969.
- ^ Otera H, Wang C, Cleland MM, Setoguchi K, Yokota S, Youle RJ, Mihara K (December 2010). "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. doi:10.1083/jcb.201007152. PMC 3002033. PMID 21149567.
- ^ Chen L, Winger AJ, Knowlton AA (2014-08-08). "Mitochondrial dynamic changes in health and genetic diseases". Molecular Biology Reports. 41 (11): 7053–7062. doi:10.1007/s11033-014-3663-y. ISSN 0301-4851. PMC 5683169. PMID 25103020.
Further reading
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