Research Grants 09/07749-1 - Biogênese, Mitocôndrias - BV FAPESP
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A putative new pos-translational modification of mitochondrial polypeptides

Grant number: 09/07749-1
Support Opportunities:Regular Research Grants
Start date: September 01, 2009
End date: August 31, 2011
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

Abstract

Previously, we have characterized a number of yeast genes involved in mitochondrial biogenesis, such as COX23, COX24,COQ9,COQ10,ATP25 and COX21. COX21 has a clear a effect in mitochondrial gene products: Atp8p and Cox2p. After the isolation of cox21 temperature sensitive alleles we observed a rapid turnover of recent synthesized Atp8p and Cox2p changed its eletrophoretical properties, suggesting that Cox21p may act in a novel pos-translational modification of these polypeptides. We also identified PET112 as a multicopy suppressor of cox21 respiratory deficient alleles. Pet112p function was recently related to the formation of a complex that together with Her2p and Cox21p work in the transamidation glutamyl-tRNA Gln generating glutamynil-tRNA Gln (Frenchin et al. Genes & Development 23:1119-1130). In fact, bacterial Pet112p belong to the well studied complex GatABC, but the function of this complex in organelles was unclear until this publication, because there were good indications that cytossolic glutamynil-tRNA sintetase would work in mitochondria as well, and the transamidation reaction would be unnecessary.In this project we will pursue if Cox21-Pet112-Her2p complex work in a second mitochondrial function promoting pos-translational modifications of Atp8 and Cox2p. This is a very important point, since with the revelation of the existence of the complex Cox21-Pet112-Her2p, someone can argue that the observed Cox21p phenotypes (degradation of Atp8p and changing of Cox2p properties) are in fact due to the mischarging of tRNAGln with glutamic, and for some special reason Cox2p and Atp8p would be more sensitive and more promptly detected. We believe that with the study of cytossolic tRNA sintetase for glutamine and glutamic acid , and futher studies of PET112 and HER2 we will be able to answer these questions. (AU)

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