Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells

Mutations in the human dynamin-related protein Drp1 cause mitochondria to f orm perinuclear clusters. We show here that these mitochondrial clusters co nsist of highly interconnected mitochondrial tubules. The increased connect ivity between mitochondria indicates that the balance between mitochondrial division and fusion is shifted toward fusion. Such a shift is consistent w ith a block in mitochondrial division. Immunofluorescence and subcellular f ractionation 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 transfecte d cells, in which green fluorescent protein fused to Drp1 is concentrated i n spots that mark actual mitochondrial division events. We find that purifi ed human Drp1 can self-assemble into multimeric ring-like structures with d imensions similar to those of dynamin multimers. The structural and functio nal similarities between dynamin and. Drp1 suggest that Drp1 wraps around t he constriction points of dividing mitochondria, analogous to dynamin colla rs at the necks of budding vesicles. We conclude that Drp1 contributes to m itochondrial division in mammalian cells.