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© The Rockefeller University Press, 0021-9525/1998//351 $5.00
The Journal of Cell Biology, Volume 143, Number 2, , 1998 351-358


Regular Articles

A Human Dynamin-related Protein Controls the Distribution of Mitochondria



Elena Smirnova, Dixie-Lee Shurland, Sergey N. Ryazantsev, and Alexander M. van der Bliek

Department of Biological Chemistry, UCLA School of Medicine, Los Angeles, California 90095-1737

Mitochondria exist as a dynamic tubular network with projections that move, break, and reseal in response to local environmental changes. We present evidence that a human dynamin-related protein (Drp1) is specifically required to establish this morphology. Drp1 is a GTPase with a domain structure similar to that of other dynamin family members. To identify the function of Drp1, we transiently transfected cells with mutant Drp1. A mutation in the GTPase domain caused profound alterations in mitochondrial morphology. The tubular projections normally present in wild-type cells were retracted into large perinuclear aggregates in cells expressing mutant Drp1. The morphology of other organelles was unaffected by mutant Drp1. There was also no effect of mutant Drp1 on the transport functions of the secretory and endocytic pathways. By EM, the mitochondrial aggregates found in cells that were transfected with mutant Drp1 appear as clusters of tubules rather than a large mass of coalescing membrane. We propose that Drp1 is important for distributing mitochondrial tubules throughout the cell. The function of this new dynamin-related protein in organelle morphology represents a novel role for a member of the dynamin family of proteins.

Key Words: GTPase • mitochondrial morphology • dnm1



Abbreviations used in this paper: Drp1, dynamin-related protein; GFP, green fluorescent protein; LDL, low-density lipoprotein; VSV-G, vesicular stomatitis virus glycoprotein.

Address all correspondence to Alexander M. van der Bliek, Department of Biological Chemistry, UCLA School of Medicine, PO Box 951737, Los Angeles, CA 90095-1737. Tel.: (310) 825-9779. Fax: (310) 206-5272. E-mail: avan{at}mednet.ucla.edu



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