Division versus fusion: Dnm1p and Fzo1p antagonistically regulate mitochondrial shape.
In yeast, mitochondrial division and fusion are highly regulated during growth, mating and sporulation, yet the mechanisms controlling these activities are unknown. Using a novel screen, we isolated mutants in which mitochondria lose their normal structure, and instead form a large network of interconnected tubules. These mutants, which appear defective in mitochondrial division, all carried mutations in DNM1, a dynamin-related protein that localizes to mitochondria. We also isolated mutants containing numerous mitochondrial fragments. These mutants were defective in FZO1, a gene previously shown to be required for mitochondrial fusion. Surprisingly, we found that in dnm1 fzo1 double mutants, normal mitochondrial shape is restored. Induction of Dnm1p expression in dnm1 fzo1 cells caused rapid fragmentation of mitochondria. We propose that dnm1 mutants are defective in the mitochondrial division, an activity antagonistic to fusion. Our results thus suggest that mitochondrial shape is normally controlled by a balance between division and fusion which requires Dnm1p and Fzo1p, respectively.
Sesaki
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Department of Cell Biology and Anatomy, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Jensen
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D002455:Cell Division; D003433:Crosses, Genetic; D034284:Dynamin I; D034281:Dynamins; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D005800:Genes, Fungal; D049452:Green Fluorescent Proteins; D006593:Hexokinase / Q000378:metabolism; D007425:Intracellular Membranes / Q000502:physiology* / Q000648:ultrastructure; D008164:Luminescent Proteins / Q000378:metabolism; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D024101:Mitochondrial Proteins; D016296:Mutagenesis; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins
D005656:Fungal Proteins; D008164:Luminescent Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins; D006593:Hexokinase; D034284:Dynamin I; C401395:FZO1 protein, S cerevisiae; D020558:GTP Phosphohydrolases; C094774:DNM1 protein, S cerevisiae; D034281:Dynamins