The absence of respiratory activity of coenzyme Q and its metabolic consequences. Biochemical analysis of treatment response in strains of fibroblasts

• Grant number: 10/19212-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2011
• End date: December 31, 2012
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Mario Henrique de Barros
• Grantee: Cleverson Busso
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Coenzyme Q (CoQ) is a molecule essential role in the transfer of electrons from mitochondrial respiratory chain. In all ten genes were identified (COQ1 - CoQ10) required for nuclear respiratory activity of coenzyme Q, however, not everyone has fully understood function. Recently our research group identified in Saccharomyces cerevisiae new biochemical properties promoted by the protein Coq10p, among these, the presence of a hydrophobic tunnel involved in binding with coenzyme Q and also its deleterious effect when expressed in large quantities. In addition to CoQ10, studies of overexpression of the gene COQ8 indicated that its protein at high concentrations is capable of stabilizing proteins and Coq3p Coq4p. Although all these genes show strong homologies in mammalian cells, there are no studies demonstrating the deleterious effect and overexpression of these genes in human cells. This project proposes to study the consequences of the absence of coenzyme Q in strains of human fibroblasts, as well as evaluating the effect of exogenous administration of different sized molecules of coenzyme Q Furthermore, the effect will be evaluated in large quantities COQ8 gene in strains deficient for the biosynthesis of CoQ as well as those of patients with neurodegenerative disorders. The results of these experiments may provide new insights into the role of these genes in the distribution of coenzyme Q in the human mitochondrial respiratory chain, as well as bringing new opportunities for treatment in patients with mitochondrial disorders.