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A more recent version of this article appeared on August 1, 2002
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Submitted on December 21, 2001
Revised on March 2, 2002
Accepted on May 10, 2002
1 Centro de Ciências do Ambiente - Departamento de Biologia, Universidade do Minho, 4710-057 Braga, Portugal; Imunobiologia, Instituto de Biologia Molecular e Celular (IBMC), 4150-171 Porto, Portugal; and Department of Biological Sciences, Columbia University, New York, USA
2 Escola de Ciências da Saúde, Universidade do Minho, 4710-057 Braga, Portugal
3 Imunobiologia, Instituto de Biologia Molecular e Celular (IBMC), 4150-171 Porto, Portugal
4 Department of Biological Sciences, Columbia University, New York, USA
5 Centro de Ciências do Ambiente - Departamento de Biologia, Universidade do Minho, 4710-057 Braga, Portugal
* Corresponding author. E-mail address: mcortereal{at}bio.uminho.pt.
Evidence is presented that mitochondria are implicated in the previously described programmed cell death (PCD) process induced by acetic acid in Saccharomyces cerevisiae. In yeast cells undergoing a PCD process induced by acetic acid, translocation of cytochrome c (CytC) to the cytosol and reactive oxygen species production, two events known to be pro-apoptotic in mammals, were observed. Associated to these events, reduction in oxygen consumption and in mitochondrial membrane potential was found. Enzymatic assays showed that the activity of complex bc1 was normal whereas that of cytochrome c oxidase (COX) was strongly decreased. This decrease is in accordance with the observed reduction in the amounts of COX II subunit and of cytochromes a+a3. The acetic acid-induced PCD process was found to be independent of oxidative phosphorylation since it was not inhibited by oligomycin treatment. The inability of S. cerevisiae mutant strains (lacking mitochondrial DNA, heme lyase or ATPase) to undergo acetic acid-induced PCD and in the case of the ATPase mutant (knockout in ATP10) the absence of CytC release provides further evidence that the process is mediated by a Mitochondria-Dependent Apoptotic Pathway (MDAP). The understanding of the involvement of a MDAP in S. cerevisiae PCD process will be most useful in the further elucidation of an ancestral pathway common to PCD in metazoans.
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