Identification of new regulation factors of mitochondrial translation in Saccharomyces cerevisiae

• Grant number: 22/02744-6
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): September 01, 2022
• Effective date (End): March 31, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Mario Henrique de Barros
• Grantee: Maria Antônia Kfouri Martins Soares
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

In human cells, mitochondrial respiratory complexes and mitoribosomes are the only examples of protein clusters whose formation derives from two distinct genomes. In order to achieve stoichiometric balance between the products of nuclear and mitochondrial origin, mitochondrial gene expression is finely controlled by a series of factors of nuclear origin, thus avoiding not only unnecessary energy expenditure, but also the accumulation of assembly intermediates potentially harmful to the redox balance. In this project, we sought to characterize Saccharomyces cerevisiae genes of unknown function potentially involved in mitochondrial gene expression. During the first year of the project, the in silico analysis of these genes was approached together with an overexpression strategy for the selection of toxic factors to mitochondrial translation when in excess. From these results, three genes for a detailed functional study were chosen: MRX6, AIM19 and YDL157c, involving the intramitochondrial localization of their gene products, detailed biochemical characterization, and the search for genetic or physical partners. The functional characterization of a gene is challenging since it depends on the integration of different techniques, and these three genes were chosen because they present an initial phenotype that can be better explored. Knowledge of the function of a gene is crucial for a better understanding of the cellular processes that cause health and disease. Our laboratory has experience in this type of study and proper conditions to develop it. (AU)