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Vol. 12, Issue 8, 2245-2256, August 2001
Department of Biological Chemistry, UCLA School of Medicine, Los
Angeles, California 90095-1737
Mutations in the human dynamin-related protein Drp1 cause
mitochondria to form perinuclear clusters. We show here that these mitochondrial clusters consist of highly interconnected mitochondrial tubules. The increased connectivity between mitochondria indicates that
the balance between mitochondrial division and fusion is shifted toward
fusion. Such a shift is consistent with a block in mitochondrial
division. Immunofluorescence and subcellular fractionation show that
endogenous Drp1 is localized to mitochondria, which is also consistent
with a role in mitochondrial division. A direct role in mitochondrial
division is suggested by time-lapse photography of transfected cells,
in which green fluorescent protein fused to Drp1 is concentrated in
spots that mark actual mitochondrial division events. We find that
purified human Drp1 can self-assemble into multimeric ring-like
structures with dimensions similar to those of dynamin multimers. The
structural and functional similarities between dynamin and Drp1 suggest
that Drp1 wraps around the constriction points of dividing
mitochondria, analogous to dynamin collars at the necks of budding
vesicles. We conclude that Drp1 contributes to mitochondrial division
in mammalian cells.
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