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FIS1

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FIS1
Available structures
PDBOrtholog search:PDBeRCSB
Identifiers
AliasesFIS1,TTC11, CGI-135, fission, mitochondrial 1
External IDsOMIM:609003;MGI:1913687;HomoloGene:41099;GeneCards:FIS1;OMA:FIS1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

51024

66437

Ensembl

ENSG00000214253

ENSMUSG00000019054

UniProt

Q9Y3D6

Q9CQ92

RefSeq (mRNA)

NM_016068

NM_001163243
NM_025562
NM_001347504

RefSeq (protein)

NP_057152

NP_001156715
NP_001334433
NP_079838

Location (UCSC)Chr 7: 101.24 – 101.25 MbChr 5: 136.98 – 137 Mb
PubMedsearch[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Mitochondrial fission 1 protein(FIS1) is aproteinthat in humans is encoded by theFIS1geneon chromosome 7.[5][6][7]This protein is a component of amitochondrialcomplex, the ARCosome, that promotesmitochondrial fission.[7][8]Its role in mitochondrial fission thus implicates it in the regulation of mitochondrial morphology, thecell cycle,andapoptosis.[7][8][9][10]By extension, the protein is involved in associated diseases, includingneurodegenerative diseasesandcancers.[11][12]

Structure

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The protein encoded by this gene is a 16 kDaintegral proteinsituated in theouter mitochondrial membrane(OMM).[9]It is composed of atransmembranedomain at the C-terminal and acytosolicdomain at the N-terminal.[9][13][14]The transmembrane domain anchors FIS1 in the OMM, though it has been observed to target differentcellular compartments,such as theperoxisome,depending on itshydrophobicity,charge,and length.[14][15]Meanwhile, the cytosolic domain contains a bundle of six helices, four of which contain two tandem tetratricopeptide repeat (TPR)-like motifs. These motifs form a concave surface by their combined superhelical structure and potentially bind another FIS1 protein to form adimer,or other proteins.[9][13]Moreover, the N-terminal arm can dock at, and thus obstruct, the TPR motifs, allowing the protein to exist in a dynamic equilibrium between "open" and "closed" states.[13]

Function

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FIS1 is indirectly involved in mitochondrial fission via binding dynamin-related protein 1 (DRP1).[12][15]By extension, FIS1 helps regulate the size and distribution of mitochondria in response to local demand for ATP or calcium ions.[13]In addition, mitochondrial fission may lead to release ofcytochrome C,which eventually leads tocell death.[9] In a separate apoptotic signalling pathway, FIS1 interacts withBCAP31to form a complex, the ARCosome. The ARCosome promotes cell death by bridging the mitochondria and theendoplasmic reticulum(ER), allowing FIS1 to transmit a proapoptotic signal from the mitochondria to the ER and activate procaspase-8. The ARCosome then forms a platform with procaspase-8 to increase calcium load in the mitochondria, resulting in apoptosis.[8][12] Additionally, FIS1 is involved in other modes of shaping mitochondrial morphology. For example, it interacts withTBC1D15to regulate mitochondrial morphology, particularly with regard tolysosomeandendosomefusion.[14]FIS1 also prevents mitochondria elongation, which would otherwise lead tocell cycledelay or arrest, and ultimately,senescence.Moreover, mitochondrial dysfunction results in elevatedreactive oxygen species(ROS) levels, which cause DNA damage and induce transcriptional repression, as well as inducemitophagy.[9][10]

Clinical Significance

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As a fission factor, FIS1 is associated with neurodegenerative diseases.[11][12]Stress, such as NO, can trigger aberrant mitochondrial fission andfusion,resulting in mitophagy.[9][11]For example, increased mitochondrial fragmentation and FIS1 levels were observed inAlzheimer's disease(AD) patients. Thus, FIS1 could serve as abiomarkerfor early detection of AD.[11]FIS1 is also implicated in a variety of cancers, includingacute myeloid leukemia,breast cancer,andprostate cancer.[12]

Interactions

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FIS1 has been shown tointeractwith:

References

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  1. ^abcGRCh38: Ensembl release 89: ENSG00000214253–Ensembl,May 2017
  2. ^abcGRCm38: Ensembl release 89: ENSMUSG00000019054–Ensembl,May 2017
  3. ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^Stojanovski D, Koutsopoulos OS, Okamoto K, Ryan MT (Mar 2004)."Levels of human Fis1 at the mitochondrial outer membrane regulate mitochondrial morphology".Journal of Cell Science.117(Pt 7): 1201–10.doi:10.1242/jcs.01058.PMID14996942.
  6. ^Kong D, Xu L, Yu Y, Zhu W, Andrews DW, Yoon Y, Kuo TH (Apr 2005). "Regulation of Ca2+-induced permeability transition by Bcl-2 is antagonized by Drpl and hFis1".Molecular and Cellular Biochemistry.272(1–2): 187–99.doi:10.1007/s11010-005-7323-3.PMID16010987.S2CID21452703.
  7. ^abc"Entrez Gene: FIS1 fission 1 (mitochondrial outer membrane) homolog (S. cerevisiae)".
  8. ^abcdeIwasawa R, Mahul-Mellier AL, Datler C, Pazarentzos E, Grimm S (Feb 2011)."Fis1 and Bap31 bridge the mitochondria-ER interface to establish a platform for apoptosis induction".The EMBO Journal.30(3): 556–68.doi:10.1038/emboj.2010.346.PMC3034017.PMID21183955.
  9. ^abcdefgGomes LC, Scorrano L (2008)."High levels of Fis1, a pro-fission mitochondrial protein, trigger autophagy".Biochimica et Biophysica Acta (BBA) - Bioenergetics.1777(7–8): 860–6.doi:10.1016/j.bbabio.2008.05.442.PMID18515060.
  10. ^abLee S, Park YY, Kim SH, Nguyen OT, Yoo YS, Chan GK, Sun X, Cho H (Feb 2014)."Human mitochondrial Fis1 links to cell cycle regulators at G2/M transition".Cellular and Molecular Life Sciences.71(4): 711–25.doi:10.1007/s00018-013-1428-8.PMC11113609.PMID23907611.S2CID11694077.
  11. ^abcdWang S, Song J, Tan M, Albers KM, Jia J (Jul 2012). "Mitochondrial fission proteins in peripheral blood lymphocytes are potential biomarkers for Alzheimer's disease".European Journal of Neurology.19(7): 1015–22.doi:10.1111/j.1468-1331.2012.03670.x.PMID22340708.S2CID21950507.
  12. ^abcdeTian Y, Huang Z, Wang Z, Yin C, Zhou L, Zhang L, Huang K, Zhou H, Jiang X, Li J, Liao L, Yang M, Meng F (2014)."Identification of novel molecular markers for prognosis estimation of acute myeloid leukemia: over-expression of PDCD7, FIS1 and Ang2 may indicate poor prognosis in pretreatment patients with acute myeloid leukemia".PLOS ONE.9(1): e84150.Bibcode:2014PLoSO...984150T.doi:10.1371/journal.pone.0084150.PMC3885535.PMID24416201.
  13. ^abcdLees JP, Manlandro CM, Picton LK, Tan AZ, Casares S, Flanagan JM, Fleming KG, Hill RB (Oct 2012)."A designed point mutant in Fis1 disrupts dimerization and mitochondrial fission".Journal of Molecular Biology.423(2): 143–58.doi:10.1016/j.jmb.2012.06.042.PMC3456991.PMID22789569.
  14. ^abcdOnoue K, Jofuku A, Ban-Ishihara R, Ishihara T, Maeda M, Koshiba T, Itoh T, Fukuda M, Otera H, Oka T, Takano H, Mizushima N, Mihara K, Ishihara N (Jan 2013)."Fis1 acts as a mitochondrial recruitment factor for TBC1D15 that is involved in regulation of mitochondrial morphology".Journal of Cell Science.126(Pt 1): 176–85.doi:10.1242/jcs.111211.PMID23077178.
  15. ^abcPalmer CS, Elgass KD, Parton RG, Osellame LD, Stojanovski D, Ryan MT (Sep 2013)."Adaptor proteins MiD49 and MiD51 can act independently of Mff and Fis1 in Drp1 recruitment and are specific for mitochondrial fission".The Journal of Biological Chemistry.288(38): 27584–93.doi:10.1074/jbc.M113.479873.PMC3779755.PMID23921378.
  16. ^Yoon Y, Krueger EW, Oswald BJ, McNiven MA (Aug 2003)."The mitochondrial protein hFis1 regulates mitochondrial fission in mammalian cells through an interaction with the dynamin-like protein DLP1".Molecular and Cellular Biology.23(15): 5409–20.doi:10.1128/MCB.23.15.5409-5420.2003.PMC165727.PMID12861026.

Further reading

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