Alexander A. Tzagoloff
Short Research Description
Energy coupling mechanisms.
Full Research Description
Web companion to the paper: "SIT4 Regulation of Respiration in S. cerevisiae"
Propagation of mitochondria depends on the expression of a small number of mitochondrial genes and a much larger pool of genetic information resident in nuclear DNA. Current estimates suggest that in the budding yeast Saccharomyces cerevisiae, close to 400 nuclear genes (referred to as PET genes) encode proteins with functions directly relevant to the maintenance of respiring mitochondria. While the functions of the mitochondrial gene products are well understood, the same cannot be said of the nuclear counterparts. An unexpectedly large proportion of PET genes have turned out to selectively affect the synthesis of individual respiratory complexes such as cytochrome oxidase and the proton translocating ATPase complex. In addition to coding for known subunit polypeptides of these heteroligomeric enzymes, PET genes govern processing of mitochondrial pre-mRNAs, translation of the mature mRNAs, and a host of post- translational events crucial for the production of the final active complexes. The functions of nuclear gene products involved in promoting late steps in assembly of the respiratory chain complexes, ensuing translation, import, and membrane insertion of all the constituents are the main focus of ongoing studies in our laboratory.
Representative Publications
- Rak, M., Gokova, S. and Tzagoloff, A. (2011) Modular assembly of yeast mitochondrial ATP synthase. EMBO J. 30: 920-930.
- Zampol, M. A., Busso, C., Gomes, F., Ferreira-Junior, J. R., Tzagoloff, A., and Barros, M. H. (2010) Over-expression of COQ10 in Saccharomyces cerevisiae inhibits mitochondrial respiration. Biochem. Biophys. Res. Commun. 402: 82-87.
- Busso, C., Tahara, E,. B., Ogusucu, R., Augusto, O., Ferreira-Junior, J. R., Tzagoloff, A., Kowaltowski, A. J., and Barros, M. H. (2010) Saccharomyces cerevisiae coq10 mutants are responsive to antimycin A. FEBS Journal, 277: 4530-4538.
- Burnichon, N., Briere, J. J., Libe, R., Vescovo, L., Riviere, J., Tissier, F., Jouanno, E., Jeunemaitre, X., Benit, P., Tzagoloff, A., Rustin, P., Bertherat, J., Favier, J., Gimenez- (2010) SDHA is a tumor suppressor gene causing paraganglioma. Hum. Molec. Genet 18: 3011-3020.
- Rak, M,, and Tzagoloff, A. (2009) F1-dependent translation of mitochondrially encoded Atp6p and Atp8p subunits of yeast ATP synthase. Proc. Natl. Acad. Sci. U.S.A. 106: 18509-18514.