Abstract
Yeast cells with the mdm10 mutation possess giant spherical mitochondria and are defective for mitochondrial inheritance. The giant mitochondria display classical features of mitochondrial ultrastructure, yet they appear incapable of movement or division. Genetic analysis indicated that the mutant phenotypes resulted from a single nuclear mutation, and the isolated MDM10 gene restored wild-type mitochondrial distribution and morphology when introduced into mutant cells. MDM10 encodes a protein of 56.2 kD located in the mitochondrial outer membrane. Depletion of Mdm10p from cells led to a condensation of normally extended, tubular mitochondria into giant spheres, and reexpression of the protein resulted in a rapid restoration of normal mitochondrial morphology. These results demonstrate that Mdm10p can control mitochondrial morphology, and that it plays a role in the inheritance of mitochondria.
Full Text
The Full Text of this article is available as a PDF (2.9 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Atencio D. P., Yaffe M. P. MAS5, a yeast homolog of DnaJ involved in mitochondrial protein import. Mol Cell Biol. 1992 Jan;12(1):283–291. doi: 10.1128/mcb.12.1.283. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Attardi G., Schatz G. Biogenesis of mitochondria. Annu Rev Cell Biol. 1988;4:289–333. doi: 10.1146/annurev.cb.04.110188.001445. [DOI] [PubMed] [Google Scholar]
- Bachmair A., Finley D., Varshavsky A. In vivo half-life of a protein is a function of its amino-terminal residue. Science. 1986 Oct 10;234(4773):179–186. doi: 10.1126/science.3018930. [DOI] [PubMed] [Google Scholar]
- Baker K. P., Schaniel A., Vestweber D., Schatz G. A yeast mitochondrial outer membrane protein essential for protein import and cell viability. Nature. 1990 Dec 13;348(6302):605–609. doi: 10.1038/348605a0. [DOI] [PubMed] [Google Scholar]
- Bordier C. Phase separation of integral membrane proteins in Triton X-114 solution. J Biol Chem. 1981 Feb 25;256(4):1604–1607. [PubMed] [Google Scholar]
- Chen L. B. Mitochondrial membrane potential in living cells. Annu Rev Cell Biol. 1988;4:155–181. doi: 10.1146/annurev.cb.04.110188.001103. [DOI] [PubMed] [Google Scholar]
- Chevallier M. R., Bloch J. C., Lacroute F. Transcriptional and translational expression of a chimeric bacterial-yeast plasmid in yeasts. Gene. 1980 Oct;11(1-2):11–19. doi: 10.1016/0378-1119(80)90082-7. [DOI] [PubMed] [Google Scholar]
- Daum G., Böhni P. C., Schatz G. Import of proteins into mitochondria. Cytochrome b2 and cytochrome c peroxidase are located in the intermembrane space of yeast mitochondria. J Biol Chem. 1982 Nov 10;257(21):13028–13033. [PubMed] [Google Scholar]
- Drubin D. G., Jones H. D., Wertman K. F. Actin structure and function: roles in mitochondrial organization and morphogenesis in budding yeast and identification of the phalloidin-binding site. Mol Biol Cell. 1993 Dec;4(12):1277–1294. doi: 10.1091/mbc.4.12.1277. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fujiki Y., Hubbard A. L., Fowler S., Lazarow P. B. Isolation of intracellular membranes by means of sodium carbonate treatment: application to endoplasmic reticulum. J Cell Biol. 1982 Apr;93(1):97–102. doi: 10.1083/jcb.93.1.97. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gbelská Y., Subík J., Svoboda A., Goffeau A., Kovác L. Intramitochondrial ATP and cell functions: yeast cells depleted of intramitochondrial ATP lose the ability to grow and multiply. Eur J Biochem. 1983 Feb 1;130(2):281–286. doi: 10.1111/j.1432-1033.1983.tb07148.x. [DOI] [PubMed] [Google Scholar]
- Guan K., Farh L., Marshall T. K., Deschenes R. J. Normal mitochondrial structure and genome maintenance in yeast requires the dynamin-like product of the MGM1 gene. Curr Genet. 1993 Jul-Aug;24(1-2):141–148. doi: 10.1007/BF00324678. [DOI] [PubMed] [Google Scholar]
- Heggeness M. H., Simon M., Singer S. J. Association of mitochondria with microtubules in cultured cells. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3863–3866. doi: 10.1073/pnas.75.8.3863. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Inagaki T., Kobayashi S., Ozeki N., Suzuki M., Fukuzawa Y., Shimizu K., Kato K., Kato K. Ultrastructural identification of light microscopic giant mitochondria in alcoholic liver disease. Hepatology. 1992 Jan;15(1):46–53. doi: 10.1002/hep.1840150110. [DOI] [PubMed] [Google Scholar]
- Ito H., Fukuda Y., Murata K., Kimura A. Transformation of intact yeast cells treated with alkali cations. J Bacteriol. 1983 Jan;153(1):163–168. doi: 10.1128/jb.153.1.163-168.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jensen R. E., Yaffe M. P. Import of proteins into yeast mitochondria: the nuclear MAS2 gene encodes a component of the processing protease that is homologous to the MAS1-encoded subunit. EMBO J. 1988 Dec 1;7(12):3863–3871. doi: 10.1002/j.1460-2075.1988.tb03272.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jones B. A., Fangman W. L. Mitochondrial DNA maintenance in yeast requires a protein containing a region related to the GTP-binding domain of dynamin. Genes Dev. 1992 Mar;6(3):380–389. doi: 10.1101/gad.6.3.380. [DOI] [PubMed] [Google Scholar]
- Koning A. J., Lum P. Y., Williams J. M., Wright R. DiOC6 staining reveals organelle structure and dynamics in living yeast cells. Cell Motil Cytoskeleton. 1993;25(2):111–128. doi: 10.1002/cm.970250202. [DOI] [PubMed] [Google Scholar]
- Kovácová V., Irmlerová J., Kovác L. Oxidative phosphorylatiion in yeast. IV. Combination of a nuclear mutation affecting oxidative phosphorylation with cytoplasmic mutation to respiratory deficiency. Biochim Biophys Acta. 1968 Aug 20;162(2):157–163. doi: 10.1016/0005-2728(68)90097-2. [DOI] [PubMed] [Google Scholar]
- Kunkel T. A., Roberts J. D., Zakour R. A. Rapid and efficient site-specific mutagenesis without phenotypic selection. Methods Enzymol. 1987;154:367–382. doi: 10.1016/0076-6879(87)54085-x. [DOI] [PubMed] [Google Scholar]
- Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
- Lauffer L., Garcia P. D., Harkins R. N., Coussens L., Ullrich A., Walter P. Topology of signal recognition particle receptor in endoplasmic reticulum membrane. 1985 Nov 28-Dec 4Nature. 318(6044):334–338. doi: 10.1038/318334a0. [DOI] [PubMed] [Google Scholar]
- Lipman D. J., Pearson W. R. Rapid and sensitive protein similarity searches. Science. 1985 Mar 22;227(4693):1435–1441. doi: 10.1126/science.2983426. [DOI] [PubMed] [Google Scholar]
- McConnell S. J., Stewart L. C., Talin A., Yaffe M. P. Temperature-sensitive yeast mutants defective in mitochondrial inheritance. J Cell Biol. 1990 Sep;111(3):967–976. doi: 10.1083/jcb.111.3.967. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McConnell S. J., Yaffe M. P. Intermediate filament formation by a yeast protein essential for organelle inheritance. Science. 1993 Apr 30;260(5108):687–689. doi: 10.1126/science.8480179. [DOI] [PubMed] [Google Scholar]
- McConnell S. J., Yaffe M. P. Nuclear and mitochondrial inheritance in yeast depends on novel cytoplasmic structures defined by the MDM1 protein. J Cell Biol. 1992 Jul;118(2):385–395. doi: 10.1083/jcb.118.2.385. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ouellette B. F., Clark M. W., Keng T., Storms R. K., Zhong W., Zeng B., Fortin N., Delaney S., Barton A., Kaback D. B. Sequencing of chromosome I from Saccharomyces cerevisiae: analysis of a 32 kb region between the LTE1 and SPO7 genes. Genome. 1993 Feb;36(1):32–42. doi: 10.1139/g93-005. [DOI] [PubMed] [Google Scholar]
- Park E. C., Finley D., Szostak J. W. A strategy for the generation of conditional mutations by protein destabilization. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1249–1252. doi: 10.1073/pnas.89.4.1249. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith B. J., Yaffe M. P. A mutation in the yeast heat-shock factor gene causes temperature-sensitive defects in both mitochondrial protein import and the cell cycle. Mol Cell Biol. 1991 May;11(5):2647–2655. doi: 10.1128/mcb.11.5.2647. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stewart L. C., Yaffe M. P. A role for unsaturated fatty acids in mitochondrial movement and inheritance. J Cell Biol. 1991 Dec;115(5):1249–1257. doi: 10.1083/jcb.115.5.1249. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Struhl K., Stinchcomb D. T., Scherer S., Davis R. W. High-frequency transformation of yeast: autonomous replication of hybrid DNA molecules. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1035–1039. doi: 10.1073/pnas.76.3.1035. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tandler B., Hoppel C. L. Studies on giant mitochondria. Ann N Y Acad Sci. 1986;488:65–81. doi: 10.1111/j.1749-6632.1986.tb46548.x. [DOI] [PubMed] [Google Scholar]
- Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Whyte W., Keopp L. H., Lamb J., Crowley J. C., Kaback D. B. Molecular cloning of chromosome I DNA from Saccharomyces cerevisiae: isolation, characterization and regulation of the SPO7 sporulation gene. Gene. 1990 Oct 30;95(1):65–72. doi: 10.1016/0378-1119(90)90414-m. [DOI] [PubMed] [Google Scholar]
- Yaffe M. P. Analysis of mitochondrial function and assembly. Methods Enzymol. 1991;194:627–643. doi: 10.1016/0076-6879(91)94046-f. [DOI] [PubMed] [Google Scholar]
- Yaffe M. P. Organelle inheritance in the yeast cell cycle. Trends Cell Biol. 1991 Dec;1(6):160–164. doi: 10.1016/0962-8924(91)90017-4. [DOI] [PubMed] [Google Scholar]
- Yaffe M. P., Schatz G. Two nuclear mutations that block mitochondrial protein import in yeast. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4819–4823. doi: 10.1073/pnas.81.15.4819. [DOI] [PMC free article] [PubMed] [Google Scholar]