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The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast

Abstract

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.

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Figure 1: Mitochondrial membranes form nets in dnm1 mutant cells.
Figure 2: Mitochondrial-membrane morphology in dnm1Δ and dnm1Δ mdm20Δ mutant cells.
Figure 3: Transmission electron microscopy and serial reconstruction of a mitochondrial net.
Figure 4: Dnm1 localizes to mitochondrial constriction sites and mitochondrial tips.
Figure 5: dnm1 mutations block mitochondrial fragmentation in fzo1-1 cells.
Figure 6: Mitochondrial-membrane morphology in dnm1 and dnm1 fzo1-1 mutant cells.
Figure 7: Mitochondrial fusion is not restored in dnm1 fzo1-1 cells.

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Acknowledgements

We thank D. Otsuga for identifying the net phenotype in the dnm1 mutant.This work was supported by grants from the NIH and the American Cancer Society (to J.M.S.) and a grant from the NSF (to J.N.).

Correspondence and requests for materials should be addressed to J.M.S.

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Correspondence to Janet M. Shaw.

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Bleazard, W., McCaffery, J., King, E. et al. The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast. Nat Cell Biol 1, 298–304 (1999). https://doi.org/10.1038/13014

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