6jfk

Structural highlights

Disease

MFN2_HUMAN Multiple symmetric lipomatosis;Autosomal dominant Charcot-Marie-Tooth disease type 2A2;Severe early-onset axonal neuropathy due to MFN2 deficiency;Hereditary motor and sensory neuropathy type 5;Hereditary motor and sensory neuropathy type 6. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.

Function

MFN2_HUMAN Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion (PubMed:11181170, PubMed:11950885, PubMed:28114303). Mitochondria are highly dynamic organelles, and their morphology is determined by the equilibrium between mitochondrial fusion and fission events (PubMed:28114303). Overexpression induces the formation of mitochondrial networks (PubMed:28114303). Membrane clustering requires GTPase activity and may involve a major rearrangement of the coiled coil domains (Probable). Plays a central role in mitochondrial metabolism and may be associated with obesity and/or apoptosis processes (By similarity). Plays an important role in the regulation of vascular smooth muscle cell proliferation (By similarity). Involved in the clearance of damaged mitochondria via selective autophagy (mitophagy) (PubMed:23620051). Is required for PRKN recruitment to dysfunctional mitochondria (PubMed:23620051). Involved in the control of unfolded protein response (UPR) upon ER stress including activation of apoptosis and autophagy during ER stress (By similarity). Acts as an upstream regulator of EIF2AK3 and suppresses EIF2AK3 activation under basal conditions (By similarity).[UniProtKB:Q80U63][UniProtKB:Q8R500]^{[1] [2] [3] [4] [5]}

References

1. ↑ Santel A, Fuller MT. Control of mitochondrial morphology by a human mitofusin. J Cell Sci. 2001 Mar;114(Pt 5):867-74. PMID:11181170
2. ↑ Rojo M, Legros F, Chateau D, Lombes A. Membrane topology and mitochondrial targeting of mitofusins, ubiquitous mammalian homologs of the transmembrane GTPase Fzo. J Cell Sci. 2002 Apr 15;115(Pt 8):1663-74. PMID:11950885
3. ↑ Chen Y, Dorn GW 2nd. PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science. 2013 Apr 26;340(6131):471-5. doi: 10.1126/science.1231031. PMID:23620051 doi:http://dx.doi.org/10.1126/science.1231031
4. ↑ Sawyer SL, Cheuk-Him Ng A, Innes AM, Wagner JD, Dyment DA, Tetreault M, Majewski J, Boycott KM, Screaton RA, Nicholson G. Homozygous mutations in MFN2 cause multiple symmetric lipomatosis associated with neuropathy. Hum Mol Genet. 2015 Sep 15;24(18):5109-14. doi: 10.1093/hmg/ddv229. Epub 2015 Jun, 17. PMID:26085578 doi:http://dx.doi.org/10.1093/hmg/ddv229
5. ↑ Cao YL, Meng S, Chen Y, Feng JX, Gu DD, Yu B, Li YJ, Yang JY, Liao S, Chan DC, Gao S. MFN1 structures reveal nucleotide-triggered dimerization critical for mitochondrial fusion. Nature. 2017 Feb 16;542(7641):372-376. doi: 10.1038/nature21077. Epub 2017 Jan, 23. PMID:28114303 doi:http://dx.doi.org/10.1038/nature21077