Aspirin commits yeast cells to apoptosis depending on carbon source

Balzan, Rena; Sapienza, Karen; Galea, Dolores R.; Vassallo, Neville; Frey, Hank; Bannister, W.H.

doi:10.1099/mic.0.26578-0

Cited by 67 publications

(79 citation statements)

References 20 publications

(18 reference statements)

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“…Interestingly, none of the examined yeasts grew in media containing 10 mM salicylate as the sole carbon source. Since acetylsalicylate (aspirin) induces apoptosis-like cell death in S. cerevisiae (Balzan et al, 2004) and exhibits antifungal properties in a number of yeast species (Leeuw et al, 2007), we analysed whether the absence of growth of C. parapsilosis on salicylate is due to its inhibitory effect on the growth or inability of this yeast to utilize salicylate as the sole carbon source (Fig. 2b).…”

Section: Resultsmentioning

confidence: 99%

Gentisate and 3-oxoadipate pathways in the yeast Candida parapsilosis: identification and functional analysis of the genes coding for 3-hydroxybenzoate 6-hydroxylase and 4-hydroxybenzoate 1-hydroxylase

et al. 2011

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The pathogenic yeast Candida parapsilosis degrades various hydroxy derivatives of benzenes and benzoates by the gentisate and 3-oxoadipate pathways. We identified the genes MNX1, MNX2, MNX3, GDX1, HDX1 and FPH1 that code for enzymes involved in these pathways in the complete genome sequence of C. parapsilosis. Next, we demonstrated that MNX1, MNX2, MNX3 and GDX1 are inducible and transcriptionally controlled by hydroxyaromatic substrates present in cultivation media. Our results indicate that MNX1 and MNX2 code for flavoprotein monooxygenases catalysing the first steps in the 3-oxoadipate and gentisate pathways, respectively (i.e. 4-hydroxybenzoate 1-hydroxylase and 3-hydroxybenzoate 6-hydroxylase). Moreover, we found that the two pathways differ by their intracellular localization. The enzymes of the 3-oxoadipate pathway, Mnx1p and Mnx3p, localize predominantly in the cytosol. In contrast, intracellular localization of the components of the gentisate pathway, Mnx2p and Gdx1p, depends on the substrate in the cultivation medium. In cells growing on glucose these proteins localize in the cytosol, whereas in media containing hydroxyaromatic compounds they associate with mitochondria. Finally, we showed that the overexpression of MNX1 or MNX2 increases the tolerance of C. parapsilosis cells to the antifungal drug terbinafine.

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Section: Resultsmentioning

confidence: 99%

Gentisate and 3-oxoadipate pathways in the yeast Candida parapsilosis: identification and functional analysis of the genes coding for 3-hydroxybenzoate 6-hydroxylase and 4-hydroxybenzoate 1-hydroxylase

et al. 2011

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“…sod2) were identified as hypersensitive for SFK1-mediated death. Accordingly, deletion of SOD2 leads to a decrease in life span (see below) and susceptibility to various redox stresses [34].…”

Section: Drug-induced Cell Deathmentioning

confidence: 99%

The mitochondrial pathway in yeast apoptosis

et al. 2007

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Mitochondria are not only important for the energetic status of the cell, but are also the fatal organelles deciding about cellular life and death. Complex mitochondrial features decisive for cell death execution in mammals are present and functional in yeast: AIF and cytochrome c release to the cytosol, mitochondrial fragmentation as well as mitochondrial hyperpolarisation followed by an oxidative burst, and breakdown of mitochondrial membrane potential. The easy accessibility of mitochondrial manipulations such as repression of respiration by growing yeast on glucose or deletion of mitochondrial DNA (rho 0 ) on the one hand and the unique ability of yeast cells to grow on nonfermentable carbon sources by switching on mitochondrial respiration on the other hand have made yeast an excellent tool to delineate the necessity for mitochondria in cell death execution. Yeast research indicates that the connection between mitochondria and apoptosis is intricate, as abrogation of mitochondrial function can be either deleterious or beneficial for the cell depending on the specific context of the death scenario. Surprisingly, mitochondrion dependent yeast apoptosis currently helps to understand the aetiology (or the complex biology) of lethal cytoskeletal alterations, ageing and neurodegeneration. For example, mutation of mitochondrial superoxide dismutase or CDC48/VCP mutations, both T. Eisenberg · S. Büttner · F. Madeo ( ) Institute of Molecular Biosciences, Universitaetsplatz 2, University of Graz, 8010 Graz, Austria e-mail: frank.madeo@uni-graz.at G. Kroemer Apoptosis, Cancer, and Immunity Unit, Institut Gustave Roussy, Faculté Paris Sud-Université, Institut National de la Santé et de la Recherche Médicale, Paris XI, France implicated in several neurodegenerative disorders, are associated with mitochondrial impairment and apoptosis in yeast.

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“…We showed that aspirin-treated MnSOD-deficient yeast cells died through a late apoptotic process when cultivated on the non-fermentable carbon source ethanol. Aspirin was found to act as an antioxidant until the appearance of apoptosis (Balzan et al, 2004). However, aspirin caused an early shift in the redox environment, due to depletion of NADPH and NADP + , which led to a dramatic drop in the GSH/GSSG concentration ratio (Sapienza & Balzan, 2005).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial involvement in aspirin-induced apoptosis in yeast

2008

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We have previously reported that aspirin induces apoptosis in manganese superoxide dismutase (MnSOD)-deficient Saccharomyces cerevisiae cells when cultivated on the non-fermentable carbon source ethanol. Here, we investigated the role of mitochondria in aspirin-induced apoptosis. We report that aspirin had an inhibitory effect on cellular respiration, and caused the release of most of the mitochondrial cytochrome c and a dramatic drop in the mitochondrial membrane potential (DY m ). Also, aspirin reduced the intracellular cytosolic pH in the MnSODdeficient cells growing in ethanol medium, but this did not seem to be the initial trigger that committed these cells to aspirin-induced apoptosis. Furthermore, loss of DY m was not required for aspirin-induced release of cytochrome c, since the initial release of cytochrome c occurred prior to the disruption of the DY m . It is thus possible that cytochrome c release does not involve the early onset of the mitochondrial permeability transition, but only an alteration of the permeability of the outer mitochondrial membrane.

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Aspirin commits yeast cells to apoptosis depending on carbon source

Cited by 67 publications

References 20 publications

Gentisate and 3-oxoadipate pathways in the yeast Candida parapsilosis: identification and functional analysis of the genes coding for 3-hydroxybenzoate 6-hydroxylase and 4-hydroxybenzoate 1-hydroxylase

Gentisate and 3-oxoadipate pathways in the yeast Candida parapsilosis: identification and functional analysis of the genes coding for 3-hydroxybenzoate 6-hydroxylase and 4-hydroxybenzoate 1-hydroxylase

The mitochondrial pathway in yeast apoptosis

Mitochondrial involvement in aspirin-induced apoptosis in yeast

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