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 outer mitochondrial membrane at sites where organelle division occurs. Although these Dnm1p-containing complexes are thought to trigger constriction and fission, little is known about their composition and assembly, and molecules...

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Bibliographic Details
Published in:	The Journal of cell biology 2000-10, Vol.151 (2), p.367-379
Main Authors:	Mozdy, A. D., McCaffery, J. M., Shaw, J. M.
Format:	Article
Language:	eng
Subjects:	Alleles Cell division Cells Dynamins Gene expression regulation Genes Genes, Fungal Genetic mutation GTP Phosphohydrolases - genetics GTP Phosphohydrolases - metabolism Intracellular Membranes Membrane Fusion Membrane Proteins - genetics Membrane Proteins - metabolism Membranes Mitochondria Mitochondria - physiology Mitochondrial DNA Mitochondrial membranes Mitochondrial Proteins Models, Biological Multigene Family Mutation Original P branes Protein Conformation Proteins Saccharomyces cerevisiae - physiology Saccharomyces cerevisiae Proteins String theory Suppression, Genetic Yeast Yeasts
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Summary:	Yeast Dnm1p is a soluble, dynamin-related GTPase that assembles on the outer mitochondrial membrane at sites where organelle division occurs. Although these Dnm1p-containing complexes are thought to trigger constriction and fission, little is known about their composition and assembly, and molecules required for their membrane recruitment have not been isolated. Using a genetic approach, we identified two new genes in the fission pathway, FIS1 and FIS2. FIS1 encodes a novel, outer mitochondrial membrane protein with its amino terminus exposed to the cytoplasm. Fis1p is the first integral membrane protein shown to participate in a eukaryotic membrane fission event. In a related study, it was shown that the FIS2 gene product (called Mdv1p) colocalizes with Dnm1p on mitochondria. Genetic and morphological evidence indicate that Fis1p, but not Mdv1p, function is required for the proper assembly and distribution of Dnm1p-containing fission complexes on mitochondrial tubules. We propose that mitochondrial fission in yeast is a multistep process, and that membrane-bound Fis1p is required for the proper assembly, membrane distribution, and function of Dnm1p-containing complexes during fission.
ISSN:	0021-9525 1540-8140