| Symbol: | MFN2 |
| UniProt: | [O95140](https://www.uniprot.org/uniprot/O95140) |
| Gene: | [MFN2](/entities/mfn2) |
| Molecular Weight: | 86 kDa |
| Location: | Outer mitochondrial membrane, ER-mitochondria contact sites |
| PDB: | [5GOP](https://www.rcsb.org/structure/5GOP) |
Mitofusin 2 (MFN2) is a dynamin-like GTPase that mediates mitochondrial outer membrane fusion and tethers mitochondria to the endoplasmic reticulum (ER) at mitochondria-ER contact sites (MAMs). Mutations in MFN2 cause Charcot-Marie-Tooth disease type 2A, and dysregulation contributes to neurodegeneration in Alzheimer's disease, Parkinson's disease, and ALS.[1][2]
MFN2 shares structural homology with MFN1 but has distinct features:
MFN2 can form both homotypic and heterotypic complexes with MFN1.[3]
MFN2 performs outer membrane fusion via:
MFN2 uniquely tethers mitochondria to the ER:[4]
MFN2 is essential for PINK1/Parkin-mediated mitophagy:[5]
Over 100 MFN2 mutations cause CMT2A:[6]
MFN2 dysfunction in AD:[7]
MFN2's role in PD:[8]
Mitochondrial dynamics disruption in ALS:[9]
Approaches to restore MFN2 function:[10]
Chen H et al. Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. Journal of Cell Biology. 2003. ↩︎
Züchner S et al. Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nature Genetics. 2004. ↩︎
Cao YL et al. MFN1 structures reveal nucleotide-triggered fusion of mitochondrial outer membrane. Nature. 2017. ↩︎
de Brito OM, Scorrano L. Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature. 2008. ↩︎
Chen Y, Dorn GW 2nd. PINK1-phosphorylated mitofusin 2 is a Parkin receptor for damaged mitochondria. Science. 2013. ↩︎
Verhoeven K et al. MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2. Brain. 2006. ↩︎
Area-Gomez E et al. Upregulated function of mitochondria-associated ER membranes in Alzheimer disease. EMBO Journal. 2012. ↩︎
Yun J et al. MUL1 acts in parallel to the PINK1/parkin pathway in regulating mitofusin and compensates for loss of PINK1/parkin. eLife. 2014. ↩︎
Manfredi G, Kawamata H. Mitochondria in neurodegeneration and the neuroprotective potential of mitochondrial biology. Advances in Experimental Medicine and Biology. 2016. ↩︎
Rocha M et al. Mitofusins: therapeutic targets for Parkinson's disease?. Neural Regeneration Research. 2018. ↩︎