A human dynamin-related protein controls the distribution of mitochondria.
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.
Smirnova
E
E
Department of Biological Chemistry, UCLA School of Medicine, Los Angeles, California 90095-1737, USA.
Shurland
D L
DL
Ryazantsev
S N
SN
van der Bliek
A M
AM
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D019556:COS Cells / Q000737:chemistry / Q000648:ultrastructure; D003001:Cloning, Molecular; D003594:Cytoplasmic Granules / Q000737:chemistry / Q000378:metabolism; D034284:Dynamin I; D034281:Dynamins; D004705:Endocytosis / Q000502:physiology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008854:Microscopy, Electron; D008870:Microtubules / Q000502:physiology*; D008928:Mitochondria / Q000201:enzymology* / Q000648:ultrastructure; D024101:Mitochondrial Proteins; D016296:Mutagenesis / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D014162:Transfection
D005656:Fungal Proteins; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D034284:Dynamin I; D020558:GTP Phosphohydrolases; C094774:DNM1 protein, S cerevisiae; D034281:Dynamins