Cytoplasmic Inheritance of Rutamycin Resistance in Mammalian Cells
The yeast Saccharomyces cerevisiae has proven the most informative model organism for the study of mitochondrial biogenesis and genetics. This is attributed to its ability to grow anaerobically and therefore without mitochondrial respiration. It was its ability to grow in the absence of mitochondrial protein synthesis that initially led Slonimski and colleagues (Coen et al., 1970) to seek mutants resistant to inhibitors of this process. In the last 10–15 years a rich library of information on mitochondrial genetics has been accumulated, so that the mitochondrial genome has probably become the best understood of eukaryotic genomes. The yeast mitochondrial genome is 70–76 kb in size and codes for the two ribosomal RNAs, 24 tRNAs, cytochrome b, three cytochrome oxidase peptides, and at least two ATPase peptides, as well as at least one ribosomal (Var) protein (Schatz and Mason, 1974; Borst and Grivell, 1978; Locker and Rabinowitz, 1979; Tzagoloff et al., 1979). The vast majority of the mitochondrial proteins are specified by the nuclear genome, are synthesized in the cytoplasm, in some cases as larger precursors, and are specifically imported into the mitochondria (Schatz, 1979). Several but not all of the yeast mitochondrial genomes contain intervening sequences (Bos et al., 1978; Haid et al., 1979; Bonitz et al., 1980). Indeed the complete nucleotide sequence of most of these genes has now been determined. A substantial portion of the yeast mitochondrial genome appears to consist of spacer DNA, whose role, if any, is unclear. Recombination between mitochondrial DNA molecules has been unequivocally demonstrated (Lewin et al., 1979).
KeywordsMitochondrial Genome Lactic Acid Production Chinese Hamster Cell Chloramphenicol Resistance Mitochondrial Protein Synthesis
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- Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J. H., Staden, R., and Young, I. G., 1981, Sequence and organization of the human mitochondrial genome, Nature 290:457–465.PubMedCrossRefGoogle Scholar
- Blanc, H., Wright, C. T., Bibb, M. J., Wallace, D. C., and Clayton, D. A., 1981, Mitochondrial DNA of chloramphenicol-resistant mouse cells contains a single nucleotide change in the region encoding the 3′ end of the large ribosomal RNA, Proc. Natl. Acad. Sci. USA 78:3789–3793.PubMedCrossRefGoogle Scholar
- Bogenhagen, D., and Clayton, D. A., 1974, The number of mitochondrial deoxyribonucleic acid genomes in mouse L and human cells, J. Biol. Chem. 249:7791–7795.Google Scholar
- Coen, D., Deutsch, J., Netler, P., Petrochilo, E., and Slonimski, P. P., 1970, Mitochondrial genetics. I — Methodology and phenomenology, in: Symposia of the Society for Experimental Biology, No. 24 (P. L. Miller, ed.) Cambridge University Press, London, pp. 449–496.Google Scholar
- DeJong, L., Holtrop, M., and Kroon, A. M., 1980, The biogenesis of rat-liver mitochondrial ATPase: Evidence that the N,N’-dicyclohexyl carbodiimide-binding protein is synthesized outside the mitochondria, Biochim. Biophys. Acta 606:331–337.Google Scholar
- Lichtor, T. R., 1980, Cytoplasmic inheritance of rutamycin resistance and a respiratory deficiency in mouse fibroblasts, Ph.D. Thesis, University of Chicago.Google Scholar
- Locker, J., and Rabinowitz, M., 1979, An overview of mitochondrial nucleic acids and biogenesis, in: Methods in Enzymology, Vol. 56, Biomembranes, Part G — Biogenesis of Mitochondria, Organization and Transport (S. Fleischer and L. Packer, eds.), Academic Press, New York, pp. 3–16.Google Scholar
- Sebald, W., and Wachter, E., 1978, Amino acid sequence of the putative protonophore of the energy-transducing ATPase complex, in: 29th Mossbacher Colloquium on Energy Conservation (G. Schaefer and M. Klingenberg, eds.), Springer-Verlag, Berlin, pp. 228–236.Google Scholar
- Williamson, D. H., Johnston, L. H., Richmond, K. M. V., and Game, J. C., 1977, Two aspects of mitochondrial DNA structure: The occurrence of two types of mitochondrial DNA in rat liver and the isolation from rat liver of DNA complexes of high buoyant density, in: Mitochondria 1977, Genetics and Biogenesis of Mitochondria (W. Bandlow, R. J. Schweyen, K. Wolf, and F. Kaudewitz, eds.), Walter deGruyter, Berlin, pp. 1–24.Google Scholar