© The Rockefeller University Press,
0021-9525/1997//141 $5.00
The Journal of Cell Biology, Volume 137, Number 1,
, 1997 141-153
The Yeast Gene, MDM20, Is Necessary for Mitochondrial Inheritance and Organization of the Actin Cytoskeleton
Greg J. Hermann,
Edward J. King, and
Janet M. Shaw
Department of Biology, University of Utah, Salt Lake City, Utah 84112
In Saccharomyces cerevisiae, the growing bud inherits a portion of the mitochondrial network from the mother cell soon after it emerges. Although this polarized transport of mitochondria is thought to require functions of the cytoskeleton, there are conflicting reports concerning the nature of the cytoskeletal element involved. Here we report the isolation of a yeast mutant, mdm20, in which both mitochondrial inheritance and actin cables (bundles of actin filaments) are disrupted. The MDM20 gene encodes a 93-kD polypeptide with no homology to other characterized proteins. Extra copies of TPM1, a gene encoding the actin filament–binding protein tropomyosin, suppress mitochondrial inheritance defects and partially restore actin cables in mdm20
cells. Synthetic lethality is also observed between mdm20 and tpm1 mutant strains. Overexpression of a second yeast tropomyosin, Tpm2p, rescues mutant phenotypes in the mdm20 strain to a lesser extent. Together, these results provide compelling evidence that mitochondrial inheritance in yeast is an actin-mediated process. MDM20 and TPM1 also exhibit the same pattern of genetic interactions; mutations in MDM20 are synthetically lethal with mutations in BEM2 and MYO2 but not SAC6. Although MDM20 and TPM1 are both required for the formation and/or stabilization of actin cables, mutations in these genes disrupt mitochondrial inheritance and nuclear segregation to different extents. Thus, Mdm20p and Tpm1p may act in vivo to establish molecular and functional heterogeneity of the actin cytoskeleton.
Abbreviations used in this paper: DAPI, 4',6-diamidino-2-phenylindole; DIC, differential interference contrast; DiOC6, 3,3' dihexyloxacarbocyanine; 5-FOA, 5-fluoro-orotic acid; HA, hemagglutinin; SD, synthetic dextrose; SGal, synthetic galactose; Ura, uracil.
Please address all correspondence to Janet M. Shaw, Department of Biology, University of Utah, Salt Lake City, UT 84112. Tel.: (801) 585-6205. Fax: (801) 581-4668.

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-
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-
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[Full Text]
-
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-
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-
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[Abstract]
[Full Text]
-
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(2001). Loss of the mitochondrial Hsp70 functions causes aggregation of mitochondria in yeast cells. J. Cell Sci.
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[Abstract]
[Full Text]
-
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-
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-
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(2000). Maintenance and Integrity of the Mitochondrial Genome: a Plethora of Nuclear Genes in the Budding Yeast. Microbiol. Mol. Biol. Rev.
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[Full Text]
-
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[Full Text]
-
Sandrock, T. M., Brower, S. M., Toenjes, K. A., Adams, A. E. M.
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[Full Text]
-
Yaffe, M. P.
(1999). The Machinery of Mitochondrial Inheritance and Behavior. Science
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[Abstract]
[Full Text]
-
Shepard, K. A., Yaffe, M. P.
(1999). The Yeast Dynamin-like Protein, Mgm1p, Functions on the Mitochondrial Outer Membrane to Mediate Mitochondrial Inheritance. JCB
144: 711-720
[Abstract]
[Full Text]
-
Pelloquin, L, Belenguer, P, Menon, Y, Gas, N, Ducommun, B
(1999). Fission yeast Msp1 is a mitochondrial dynamin-related protein. J. Cell Sci.
112: 4151-4161
[Abstract]
-
Catlett, N. L., Weisman, L. S.
(1998). The terminal tail region of a yeast myosin-V mediates its attachment to vacuole membranes and sites of polarized growth. Proc. Natl. Acad. Sci. USA
95: 14799-14804
[Abstract]
[Full Text]
-
Otsuga, D., Keegan, B. R., Brisch, E., Thatcher, J. W., Hermann, G. J., Bleazard, W., Shaw, J. M.
(1998). The Dynamin-related GTPase, Dnm1p, Controls Mitochondrial Morphology in Yeast. JCB
143: 333-349
[Abstract]
[Full Text]
-
Smirnova, E., Shurland, D.-L., Ryazantsev, S. N., van der Bliek, A. M.
(1998). A Human Dynamin-related Protein Controls the Distribution of Mitochondria. JCB
143: 351-358
[Abstract]
[Full Text]
-
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(1998). Mitochondrial Fusion in Yeast Requires the Transmembrane GTPase Fzo1p. JCB
143: 359-373
[Abstract]
[Full Text]
-
Belmont, L. D., Drubin, D. G.
(1998). The Yeast V159N Actin Mutant Reveals Roles for Actin Dynamics In Vivo. JCB
142: 1289-1299
[Abstract]
[Full Text]
-
Okamoto, K., Perlman, P. S., Butow, R. A.
(1998). The Sorting of Mitochondrial DNA and Mitochondrial Proteins in Zygotes: Preferential Transmission of Mitochondrial DNA to the Medial Bud. JCB
142: 613-623
[Abstract]
[Full Text]
-
Rapaport, D., Brunner, M., Neupert, W., Westermann, B.
(1998). Fzo1p Is a Mitochondrial Outer Membrane Protein Essential for the Biogenesis of Functional Mitochondria in Saccharomyces cerevisiae. J. Biol. Chem.
273: 20150-20155
[Abstract]
[Full Text]
-
Boldogh, I., Vojtov, N., Karmon, S., Pon, L. A.
(1998). Interaction between Mitochondria and the Actin Cytoskeleton in Budding Yeast Requires Two Integral Mitochondrial Outer Membrane Proteins, Mmm1p and Mdm10p. JCB
141: 1371-1381
[Abstract]
[Full Text]
-
Roeder, A. D., Hermann, G. J., Keegan, B. R., Thatcher, S. A., Shaw, J. M.
(1998). Mitochondrial Inheritance Is Delayed in Saccharomyces cerevisiae Cells Lacking the Serine/Threonine Phosphatase PTC1. Mol. Biol. Cell
9: 917-930
[Abstract]
[Full Text]
-
Bryant, N. J., Stevens, T. H.
(1998). Vacuole Biogenesis in Saccharomyces cerevisiae: Protein Transport Pathways to the Yeast Vacuole. Microbiol. Mol. Biol. Rev.
62: 230-247
[Abstract]
[Full Text]
-
Karpova, T., Moltz, S., Riles, L., Guldener, U, Hegemann, J., Veronneau, S, Bussey, H, Cooper, J.
(1998). Depolarization of the actin cytoskeleton is a specific phenotype in Saccharomyces cerevisiae. J. Cell Sci.
111: 2689-2696
[Abstract]
-
Fields, S., Conrad, M., Clarke, M
(1998). The S. cerevisiae CLU1 and D. discoideum cluA genes are functional homologues that influence mitochondrial morphology and distribution. J. Cell Sci.
111: 1717-1727
[Abstract]