In yeast, mitochondrial division and fusion are highly regulated during gro
wth, mating and sporulation, yet the mechanisms controlling these activitie
s are unknown, Using a novel screen, we isolated mutants in which mitochond
ria lose their normal structure? and instead form a large network of interc
onnected tubules, These mutants, which appear defective in mitochondrial di
vision, all carried mutations in DNM1, a dynamin-related protein that local
izes to mitochondria. We also isolated mutants containing numerous mitochon
drial fragments, These mutants were defective in FZO1, a gene previously sh
own to be required for mitochondrial fusion. Surprisingly, we found that in
dnm1 fzo1 double mutants, normal mitochondrial shape is restored, Inductio
n of Dnm1p expression in dnm1 fzo1 cells caused rapid fragmentation of mito
chondria. We propose that dnm1 mutants are defective in the mitochondrial d
ivision, an activity antagonistic to fusion. Our results thus suggest that
mitochondrial shape is normally controlled by a balance between division an
d fusion which requires Dnm1p and Fzo1p, respectively.