Catalases and thioredoxin peroxidase protect Saccharomyces cerevisiae against Ca(2+)-induced mitochondrial membrane permeabilization and cell death.
The involvement of reactive oxygen species in Ca(2+)-induced mitochondrial membrane permeabilization and cell viability was studied using yeast cells in which the thioredoxin peroxidase (TPx) gene was disrupted and/or catalase was inhibited by 3-amino-1,2, 4-triazole (ATZ) treatment. Wild-type Saccharomyces cerevisiae cells were very resistant to Ca(2+) and inorganic phosphate or t-butyl hydroperoxide-induced mitochondrial membrane permeabilization, but suffered an immediate decrease in mitochondrial membrane potential when treated with Ca(2+) and the dithiol binding reagent phenylarsine oxide. In contrast, S. cerevisiae spheroblasts lacking the TPx gene and/or treated with ATZ suffered a decrease in mitochondrial membrane potential, generated higher amounts of hydrogen peroxide and had decreased viability under these conditions. In all cases, the decrease in mitochondrial membrane potential could be inhibited by ethylene glycol-bis(beta-aminoethyl ether) N,N, N',N'-tetraacetic acid, dithiothreitol or ADP, but not by cyclosporin A. We conclude that TPx and catalase act together, maintaining cell viability and protecting S. cerevisiae mitochondria against Ca(2+)-promoted membrane permeabilization, which presents similar characteristics to mammalian permeability transition.
Kowaltowski
A J
AJ
Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, 13083-970, Campinas, Brazil.
Vercesi
A E
AE
Rhee
S G
SG
Netto
L E
LE
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000640:Amitrole / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002374:Catalase / Q000037:antagonists & inhibitors / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D004229:Dithiothreitol / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007425:Intracellular Membranes / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000502:physiology*; D009154:Mutation; D009363:Neoplasm Proteins; D010539:Permeability / Q000187:drug effects; D010544:Peroxidases / Q000235:genetics / Q000502:physiology*; D054464:Peroxiredoxins; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D004533:Egtazic Acid; D000244:Adenosine Diphosphate; D010544:Peroxidases; D054464:Peroxiredoxins; D002374:Catalase; D002118:Calcium; D004229:Dithiothreitol; D000640:Amitrole