A Human Dynamin-related Protein Controls the Distribution of Mitochondria

Smirnova, Elena A.; Shurland, Dixie-Lee; Ryazantsev, Sergey; Bliek, Alexander M. van der

doi:10.1083/jcb.143.2.351

Cited by 659 publications

(579 citation statements)

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“…Mitochondrial fission depends largely on the dynamin related protein Drp1, which is localised predominantly in the cytosol and must be recruited to mitochondria for fission to occur (Smirnova et al, 1998;Smirnova et al, 2001; Figure 2). …”

Section: Mitochondrial Fissionmentioning

confidence: 99%

Mitochondrial fission/fusion dynamics and apoptosis

2010

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Mitochondria play an important role in the progression of apoptosis through the release of pro-apoptotic factors, such as cytochrome c, from the mitochondrial intermembrane space.During this process, mitochondrial networks are dramatically reorganised from long filamentous interconnected tubules into small punctate spheres. Whether remodelling of mitochondrial networks is necessary for apoptosis-associated cytochrome c release, or merely an accompanying process, has been a subject of debate. Here we discuss evidence for and against the role of mitochondrial fragmentation in the progression of apoptosis and highlight recent advances which indicate that mitochondrial fission is not a critical requirement for apoptosis-associated cytochrome c release. We also discuss an emerging role for Bcl-2 family members as regulators of mitochondrial fission and fusion dynamics, independent of the role of this family in the regulation of apoptosis.

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Section: Mitochondrial Fissionmentioning

confidence: 99%

Mitochondrial fission/fusion dynamics and apoptosis

2010

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“…Mutations in DNM1 cause mitochondrial membranes to collapse to one side of the cell but do not interfere with the morphology or distribution of other cytoplasmic organelles 11 . A Dnm1-like molecule called Drp1 also controls the distribution of mitochondria in mammalian cells 12 . Dnm1 is structurally related to the GTPase dynamin 13 , which is required for the scission and release of clathrin-coated vesicles from the plasma membrane during endocytosis (ref.…”

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confidence: 99%

The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast

et al. 1999

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The dynamin-related GTPase Dnm1 controls mitochondrial morphology in yeast. Here we show that dnm1 mutations convert the mitochondrial compartment into a planar 'net' of interconnected tubules. We propose that this net morphology results from a defect in mitochondrial fission. Immunogold labelling localizes Dnm1 to the cytoplasmic face of constricted mitochondrial tubules that appear to be dividing and to the ends of mitochondrial tubules that appear to have recently completed division. The activity of Dnm1 is epistatic to that of Fzo1, a GTPase in the outer mitochondrial membrane that regulates mitochondrial fusion. dnm1 mutations prevent mitochondrial fragmentation in fzo1 mutant strains. These findings indicate that Dnm1 regulates mitochondrial fission, assembling on the cytoplasmic face of mitochondrial tubules at sites at which division will occur.The mitochondrion is a complex organelle with a double membrane, its own genome and an independent protein-synthetic machinery. Although the role of mitochondria in metabolism and ATP production is more widely recognized, alterations in mitochondrial shape and abundance are also important for cellular function and differentiation. For example, mitochondrial morphology and copy number change in response to nutrient availability in yeast cells 1 , cell damage and apoptosis in mammalian cells 2 and developmental cues in Xenopus and Drosophila 3,4 . Cytological studies indicate that the 'steady-state' mitochondrial morphology and copy number can vary dramatically in different cell types, ranging from multiple, spherical organelles to the branched, tubular networks found in budding yeast and some mammalian cells [5][6][7] . These differences in mitochondrial morphology and copy number are largely determined by the balance between ongoing mitochondrial fission and fusion events.Little is known about molecules that regulate mitochondrial fission and fusion. The fuzzy onions (fzo) family of transmembrane GTPases was recently shown to control mitochondrial fusion in different organisms and cell types. In Drosophila, fzo is required for a developmentally regulated mitochondrial fusion event during spermatogenesis 8 . In budding yeast, mutations in fzo1 cause mitochondrial networks to fragment 9,10 and prevent mitochondrial fusion during yeast mating 9 . Molecules required for mitochondrial fission © 1999 Macmillan Magazines Ltd § Correspondence and requests for materials should be addressed to J.M.S. shaw@bioscience.utah.edu. NIH Public Access Results Mitochondrial membranes form nets in dnm1 mutant cellsWe previously reported that mitochondrial membranes collapse to one side of the cell in a dnm1Δ mutant strain 11 . Transmission electron microscopy indicated that these collapsed membranes might be organized in an unusual structure 11 . To characterize this structure further, we studied mitochondrial morphology in dnm1Δ cells under several different conditions.As reported previously, dnm1Δ mutants grown at 25 °C lack the highly branched mitochondrial network charac...

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“…8 In mammalian cells, at least two proteins, dynamin-related protein 1 (Drp1) and hFis1, are required for mitochondrial fission. 9,10 Drp1 is a large GTPase that translocates to puncta on mitochondria, where it couples GTP hydrolysis with mitochondrial membrane constriction and fission. 10,11 How Drp1 is recruited to mitochondria to trigger fission is still unknown.…”

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confidence: 99%

“…9,10 Drp1 is a large GTPase that translocates to puncta on mitochondria, where it couples GTP hydrolysis with mitochondrial membrane constriction and fission. 10,11 How Drp1 is recruited to mitochondria to trigger fission is still unknown. However, one possibility is hFis1, a protein with a transmembrane domain that is anchored to the mitochondrial outer membrane via its Cterminal region.…”

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confidence: 99%