Mitochondrial fission factor

{{Short description|Protein-coding gene in the species Homo sapiens}}

Mitochondrial fission factor (Mff) is a protein that in humans is encoded by the MFF gene.{{cite web | title = Entrez Gene: mitochondrial fission factor| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=56947| access-date = }} 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.{{cite journal | vauthors = Otera H, Wang C, Cleland MM, Setoguchi K, Yokota S, Youle RJ, Mihara K | title = Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells | journal = The Journal of Cell Biology | volume = 191 | issue = 6 | pages = 1141–1158 | date = December 2010 | pmid = 21149567 | doi = 10.1083/jcb.201007152 | pmc = 3002033 }} 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.{{Cite journal |last1=Otera |first1=Hidenori |last2=Wang |first2=Chunxin |last3=Cleland |first3=Megan M. |last4=Setoguchi |first4=Kiyoko |last5=Yokota |first5=Sadaki |last6=Youle |first6=Richard J. |last7=Mihara |first7=Katsuyoshi |date=2010-12-13 |title=Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells |journal=Journal of Cell Biology |volume=191 |issue=6 |pages=1141–1158 |doi=10.1083/jcb.201007152 |issn=1540-8140|doi-access=free |pmid=21149567 |pmc=3002033 }} It has also been shown to regulate peroxisome morphology.{{cite journal | vauthors = Gandre-Babbe S, van der Bliek AM | title = The novel tail-anchored membrane protein Mff controls mitochondrial and peroxisomal fission in mammalian cells | journal = Molecular Biology of the Cell | volume = 19 | issue = 6 | pages = 2402–2412 | date = June 2008 | pmid = 18353969 | pmc = 2397315 | doi = 10.1091/mbc.E07-12-1287 }}

Role in 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).{{cite journal | vauthors = Otera H, Wang C, Cleland MM, Setoguchi K, Yokota S, Youle RJ, Mihara K | title = Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells | journal = The Journal of Cell Biology | volume = 191 | issue = 6 | pages = 1141–1158 | date = December 2010 | pmid = 21149567 | pmc = 3002033 | doi = 10.1083/jcb.201007152 }} 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. 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.{{Cite journal |last1=Chen |first1=Le |last2=Winger |first2=Allison J. |last3=Knowlton |first3=Anne A. |date=2014-08-08 |title=Mitochondrial dynamic changes in health and genetic diseases |url=http://dx.doi.org/10.1007/s11033-014-3663-y |journal=Molecular Biology Reports |volume=41 |issue=11 |pages=7053–7062 |doi=10.1007/s11033-014-3663-y |pmid=25103020 |issn=0301-4851|pmc=5683169 }}

Mitochondrial fission factor

Role in mitochondrial fission

References

Further reading