Dnm1p GTPase-mediated mitochondrial fission is a multi-step process requiring the novel integral membrane component Fis1p

Yeast Dnm1p is a soluble, dynamin-related GTPase that assembles on the ente r mitochondrial membrane at sites where organelle division occurs. Although these Dnm1p-containing complexes are thought to trigger constriction and f ission, little is known about their composition and assembly, and molecules required for their membrane recruitment have not been isolated. Using a ge netic approach, we identified two new genes in the fission pathway, FIS1 an d FIS2. FIS1 encodes a novel, outer mitochondrial membrane protein with its amino terminus exposed to the cytoplasm. Fis1p is the first integral membr ane protein shown to participate in a eukaryotic membrane fission event. In a related study (Tieu, Q., and J. Nunnari. 2000. J. Cell Biol. 151:353-365 ), it was shown that the FIS2 gene product (called Mdv1p) colocalizes with Dnm1p on mitochondria. Genetic and morphological evidence indicate that Fis 1p, but not Mdv1p, function is required for the proper assembly and distrib ution of Dnm1p-containing fission complexes on mitochondrial tubules. We pr opose that mitochondrial fission in yeast is a multistep process, and that membrane-bound Fis1p is required for the proper assembly, membrane distribu tion, and function of Dnm1p-containing complexes during fission.