InterPro domain: IPR033745

Fis1, along with Dnm1 and Mdv1, is an essential protein in mediating mitochondrial fission. Dnm1 and Fis1 are highly conserved, with a common mechanism in disparate species. In mutants of these proteins, mitochondrial fission is impaired, resulting in networks of undivided mitochondria. Fis1 appears to act via the recruitment of division complexes to the mitochondrial outer membrane. Dnm1 is recruited to mitochondria via interactions with the adaptor proteins Caf4 and Mdv1, which bind directly to Fis1 [ 1 , 2 ].

The Fis1 N terminus is cytosolic and tethered to the mitochondrial outer membrane via a C-terminal transmembrane domain. The cytosolic domain of Fis1 forms a six-helix bundle, in which the central four helices consist of two tandem tetratricopeptide repeat (TPR)-like motifs, known to mediate protein-protein interactions [ 3 , 4 , 5 , 6 ].

1. The machines that divide and fuse mitochondria. Annu. Rev. Biochem. 76, 751-80
2. The mitochondrial fission adaptors Caf4 and Mdv1 are not functionally equivalent. PLoS ONE 7, e53523
3. Structural basis for recruitment of mitochondrial fission complexes by Fis1. Proc. Natl. Acad. Sci. U.S.A. 104, 18526-30
4. Novel structure of the N terminus in yeast Fis1 correlates with a specialized function in mitochondrial fission. J. Biol. Chem. 280, 21444-52
5. The solution structure of human mitochondria fission protein Fis1 reveals a novel TPR-like helix bundle. J. Mol. Biol. 334, 445-58
6. Cytosolic domain of the human mitochondrial fission protein fis1 adopts a TPR fold. Proteins 54, 153-6