| Symbol: | FIS1 |
| UniProt: | [Q9Y3D6](https://www.uniprot.org/uniprot/Q9Y3D6) |
| Gene: | [FIS1](/entities/fis1) |
| Molecular Weight: | 17 kDa |
| Location: | Outer mitochondrial membrane, peroxisomal membrane |
| PDB: | [1N3A](https://www.rcsb.org/structure/1N3A), [2PQN](https://www.rcsb.org/structure/2PQN) |
Fission 1 (FIS1) is a small tail-anchored protein embedded in the outer mitochondrial membrane that serves as an adaptor for the DRP1 GTPase during mitochondrial fission. FIS1 recruits and anchors DRP1 to the mitochondrial surface, initiating the fission process that divides mitochondria. Dysregulated FIS1 expression contributes to excessive mitochondrial fragmentation in Alzheimer's disease, Parkinson's disease, and Huntington's disease.[1][2]
FIS1 has a compact architecture optimized for fission machinery recruitment:
The TPR domains create a platform that docks DRP1 and associated factors.[3]
FIS1 mediates fission through several steps:[4]
FIS1 also regulates peroxisome division:[5]
FIS1-mediated fission prepares damaged mitochondria for clearance:[6]
FIS1 is upregulated in AD with pathological consequences:[7]
Mitochondrial dynamics imbalance in PD:[8]
mHTT impacts FIS1-mediated fission:[9]
Motor neuron vulnerability involves fission:[10]
Strategies to reduce excessive FIS1 activity:
James DI et al. hFis1, a novel component of the mammalian mitochondrial fission machinery. Journal of Biological Chemistry. 2003. ↩︎
Stojanovski D et al. Levels of human Fis1 at the mitochondrial outer membrane regulate mitochondrial morphology. Journal of Cell Science. 2004. ↩︎
Dohm JA et al. Structure and small molecule interactions of the mitochondrial fission protein Fis1. Biochemistry. 2004. ↩︎
Yu T et al. Regulation of mitochondrial fission and apoptosis by the mitochondrial outer membrane protein Fis1. Journal of Cell Science. 2005. ↩︎
Koch A et al. Fis1, the mitochondrial fission regulator, is also critical for peroxisomal fission. EMBO Journal. 2004. ↩︎
Gomes LC, Scorrano L. Mitochondrial morphology in mitophagy and macroautophagy. Nature Reviews Molecular Cell Biology. 2013. ↩︎
Wang X et al. Amyloid-beta induces mitochondrial dysfunction by downregulation of mitofusin 1 and 2. Neurobiology of Aging. 2016. ↩︎
Cui M et al. Mitochondrial fission is required for distribution and transport of PINK1 into affected neurons. Journal of Cell Science. 2010. ↩︎
Kim J et al. Mitochondrial complex I inhibition accelerates mitochondrial dynamics in Huntington's disease. Cell Death & Disease. 2018. ↩︎
Song W et al. Mitochondrial fission and fusion in amyotrophic lateral sclerosis. Neurobiology of Disease. 2013. ↩︎