Study of the impact of eIF5A function on cellular processes involving mitochondria

• Grant number: 17/07881-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2018
• End date: October 31, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Cleslei Fernando Zanelli
• Grantee: Anderson Amendola Pinheiro
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

The ribosome is responsible for catalyzing protein synthesis and is supported by several translation factors at all stages of the process (initiation, elongation, termination, and recycling). Although important differences are observed in the initiation, termination and recycling phases between prokaryotes and eukaryotes, the translation elongation has conserved factors in the three major domains of life (archaea, bacteria, and eukaryotes). Recent studies have indicated the essential participation of the eIF5A factor during the translation elongation in eukaryotes, and its homologous EF-P, in prokaryotes. eIF5A has already been related to several cellular processes, such as cell cycle progression (G1/S transition), secretory pathway, apoptosis, and others, however, it is not clear how these processes are affected by eIF5A function in translation. To be active, eIF5A depends on a unique, two-stage post-translational modification, first the transfer of an aminobutyl group from spermidine to the amino group of a specific lysine by the deoxyhypusine synthase, followed by hydroxylation of this group by deoxyhypusine hydroxylase, forming the amino acid hypusine. Previous proteomic profile analysis in eIF5A mutants, using the Saccharomyces cerevisiae as a model, indicated groups of proteins with significantly altered levels, most are related to mitochondrial processes. The purpose of this work is to validate the data and help to understand the relationship between these mitochondrial processes and eIF5A.