O papel do metabolismo de ferro no estresse oxidativo em Saccharomyces cerevisiae

Author(s)

Jeane Maria de Freitas

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
• Defense date: 1999-07-26

Examining board members

Rogerio Meneghini; Beatriz Amaral de Castilho; Francisco Rafael Martins Laurindo; Francisco Gorgonio da Nobrega; Luiz Soares Netto

• Advisor: Rogerio Meneghini

Abstract

Superoxide dismutase (SOD) has a protective role against oxygen toxicity to remove superoxide radicals (O2-) through its dismutation to hydrogen peroxide and oxygen. Yeast contains two intracellular SODs, one containing manganese and the other copper and zinc in their active sites. Saccharomyces cerevisiae lacking Cu,Zn-SOD shows a serie of metabolic defects associated with increased levels of O2-. A superoxide specific damage is the release of iron from iron-sulfur clusters-containing enzymes, which lead to an inactivation of these enzymes. Since, Fe (II) and H2O2 are released from oxidized clusters, this process can favor hydroxyl radical (•OH) production in the Fenton reaction. •OH radical is a very reactive radical that causes damage to proteins, lipids and DNA. In this work, we observed an alteration in the iron metabolism in yeast cells lacking Cu,ZnSOD. Our results show a) Increased total intracellular iron content in sod1Δ strains; b) High levels of FET3 gene transcripts in the mutants (FET3 encodes a high affinity iron uptake cell membrane protein); c) Increased iron transport in the cell membrane in sod1Δ strains. This is the first evidence of an alteration in iron metabolism under SOD deficiency. We propose that sod1Δ mutants show increased iron uptake as a cells\' effort to reactivate iron sulfur-containing enzymes. (AU)