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Assembly of respiratory chain complexes, oxidative stress and regulatory mechanisms involved in their co-expression

Grant number: 07/01092-5
Support Opportunities:Regular Research Grants
Duration: August 01, 2007 - July 31, 2009
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Mario Henrique de Barros
Grantee:Mario Henrique de Barros
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


The aim goal here is to study mitochondrial metabolism involved with the biogenesis of respiratory complexes, oxidative stress and possible ways of co-regulation among different respiratory complexes. The assembly of mitochondrial complexes depends on the information of two different genomes, a hallmark not found in any other enzymatic complexes inside our cells. In previous studies of this laboratory 4 new S. cerevisiae ORFs were characterized leading to new research proposals. For instance, YOL008W was renamed as COQ10, interestingly coq10 mutants does not have coenzyme Q activity even though they have endogenous amount of this coenzyme inside their cells. We would like to study, also, the oxidative stress present in coenzyme Q mutants, and reproduce human mutations in the yeast homologues. For the very first time this laboratory will have the opportunity to use yeast as a direct model for human diseases, an opportunity that we were looking forward to have. This opportunity was offer by Dr. Michio Hirano, at Columbia University. However, in the field of unknown ORFs , we will proceed in the characterization of three other genes. One of those, YGR102C has a clear effect on cytochrome c oxidase and ATP sintase expression, which prompt us to study regulatory mechanisms involving the expression of these two complexes. In resume, this project will continue the work on mitochondria biogenesis, describing new genes, and will allow the establishment of new field in the lab, related to yeast as model for human diseases. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ZAMPOL, MARIANA A.; BUSSO, CLEVERSON; GOMES, FERNANDO; FERREIRA-JUNIOR, JOSE RIBAMAR; TZAGOLOFF, ALEXANDER; BARROS, MARIO H.. Over-expression of COQ10 in Saccharomyces cerevisiae inhibits mitochondrial respiration. Biochemical and Biophysical Research Communications, v. 402, n. 1, p. 82-87, . (07/01092-5)
BUSSO, CLEVERSON; TAHARA, ERICH B.; OGUSUCU, RENATA; AUGUSTO, OHARA; FERREIRA-JUNIOR, JOSE RIBAMAR; TZAGOLOFF, ALEXANDER; KOWALTOWSKI, ALICIA J.; BARROS, MARIO H.. Saccharomyces cerevisiae coq10 null mutants are responsive to antimycin A. FEBS Journal, v. 277, n. 21, p. 4530-4538, . (07/01092-5)

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