| Symbol: | MFN1 |
| UniProt: | Q8IWA4 |
| Gene: | MFN1 |
| Molecular Weight: | 83 kDa |
| Location: | Outer mitochondrial membrane |
| PDB: | 5GOM |
Mitofusin 1 (MFN1) is a dynamin-like GTPase embedded in the outer mitochondrial membrane that mediates mitochondrial fusion. Along with its paralog MFN2, MFN1 orchestrates the tethering and merging of adjacent mitochondria, a process essential for maintaining mitochondrial network integrity, bioenergetic efficiency, and cellular health. Defects in mitochondrial fusion contribute to neurodegeneration in Alzheimer's disease, Parkinson's disease, and Huntington's disease.[1][2]
MFN1 contains several key structural elements:
The crystal structure of MFN1 reveals a dimeric configuration that undergoes GTP-dependent conformational changes to drive membrane fusion.[3]
MFN1 mediates outer membrane fusion through a multi-step process:[4]
MFN1 often functions redundantly with MFN2, though tissue-specific expression patterns differ.
MFN1 participates in quality control by:
MFN1 expression and mitochondrial fusion are impaired in AD:[5]
Mitochondrial dynamics disruption is central to PD:[6]
Mutant huntingtin impacts mitochondrial dynamics:[7]
Strategies to enhance MFN1 activity:
Therapeutic development faces obstacles:[8]
Chen H et al. Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. Journal of Cell Biology. 2003. ↩︎
Mishra P, Chan DC. Metabolic regulation of mitochondrial dynamics. Journal of Cell Biology. 2016. ↩︎
Cao YL et al. MFN1 structures reveal nucleotide-triggered fusion of mitochondrial outer membrane. Nature. 2017. ↩︎
Koshiba T et al. Structural basis of mitochondrial tethering by mitofusin complexes. Science. 2004. ↩︎
Wang X et al. Amyloid-beta induces mitochondrial dysfunction by downregulation of mitofusin 1 and 2. Neurobiology of Aging. 2016. ↩︎
Tanaka A et al. Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. Journal of Cell Biology. 2010. ↩︎
Kim J et al. Mitochondrial complex I inhibition accelerates mitochondrial dynamics in Huntington's disease. Cell Death & Disease. 2018. ↩︎
Rocha M et al. Mitofusins: therapeutic targets for Parkinson's disease?. Neural Regeneration Research. 2018. ↩︎