Selenite-induced cell death in Saccharomyces cerevisiae: protective role of glutaredoxins.
Unlike in higher organisms, selenium is not essential for growth in Saccharomyces cerevisiae. In this species, it causes toxic effects at high concentrations. In the present study, we show that when supplied as selenite to yeast cultures growing under fermentative metabolism, its effects can be dissected into two death phases. From the time of initial treatment, it causes loss of membrane integrity and genotoxicity. Both effects occur at higher levels in mutants lacking Grx1p and Grx2p than in wild-type cells, and are reversed by expression of a cytosolic version of the membrane-associated Grx7p glutaredoxin. Grx7p can also rescue the high levels of protein carbonylation damage that occur in selenite-treated cultures of the grx1 grx2 mutant. After longer incubation times, selenite causes abnormal nuclear morphology and the appearance of TUNEL-positive cells, which are considered apoptotic markers in yeast cells. This effect is independent of Grx1p and Grx2p. Therefore, the protective role of the two glutaredoxins is restricted to the initial stages of selenite treatment. Lack of Yca1p metacaspase or of a functional mitochondrial electron transport chain only moderately diminishes apoptotic-like death by selenite. In contrast, selenite-induced apoptosis is dependent on the apoptosis-inducing factor Aif1p. In the absence of the latter, intracellular protein carbonylation is reduced after prolonged selenite treatment, supporting the supposition that part of the oxidative damage is contributed by apoptotic cells.
Izquierdo
Alicia
A
Departament de Ciències Mèdiques Bàsiques, IRBLleida, Universitat de Lleida, Montserrat Roig 2, 25008-Lleida, Spain.
Casas
Celia
C
Departament de Ciències Mèdiques Bàsiques, IRBLleida, Universitat de Lleida, Montserrat Roig 2, 25008-Lleida, Spain.
Herrero
Enrique
E
Departament de Ciències Mèdiques Bàsiques, IRBLleida, Universitat de Lleida, Montserrat Roig 2, 25008-Lleida, Spain.
D017209:Apoptosis / Q000187:drug effects*; D054477:Glutaredoxins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D018038:Sodium Selenite / Q000378:metabolism*
C532450:GRX7 protein, S cerevisiae; D054477:Glutaredoxins; C530831:Grx1 protein, S cerevisiae; C527885:Grx2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D018038:Sodium Selenite