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The Warburg effect suppresses oxidative stress induced apoptosis in a yeast model for cancer.

Ruckenstuhl C, Büttner S, Carmona-Gutierrez D, Eisenberg T, Kroemer G, Sigrist SJ, Fröhlich KU, Madeo F - PLoS ONE (2009)

Bottom Line: Research has mainly focused on a possible connection between increased glycolysis and tumor development whereas decreased respiration has largely been left unattended.Therefore, a causal relation between decreased respiration and tumorigenesis has not been demonstrated.In contrast, enhancement of respiration triggered cell death.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Biosciences, University of Graz, Graz, Austria.

ABSTRACT

Background: Otto Warburg observed that cancer cells are often characterized by intense glycolysis in the presence of oxygen and a concomitant decrease in mitochondrial respiration. Research has mainly focused on a possible connection between increased glycolysis and tumor development whereas decreased respiration has largely been left unattended. Therefore, a causal relation between decreased respiration and tumorigenesis has not been demonstrated.

Methodology/principal findings: For this purpose, colonies of Saccharomyces cerevisiae, which is suitable for manipulation of mitochondrial respiration and shows mitochondria-mediated cell death, were used as a model. Repression of respiration as well as ROS-scavenging via glutathione inhibited apoptosis and conferred a survival advantage during seeding and early development of this fast proliferating solid cell population. In contrast, enhancement of respiration triggered cell death.

Conclusion/significance: Thus, the Warburg effect might directly contribute to the initiation of cancer formation--not only by enhanced glycolysis--but also via decreased respiration in the presence of oxygen, which suppresses apoptosis.

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Related in: MedlinePlus

An oxa1 deletion does not influence the strains growth rate.(A) Growth curves of an oxa1 deletion strain and the corresponding wild-type strain. Experiment was performed in triplicate. The y-axis is scaled logarithmically. (B) Size of isolated colonies of the indicated strains grown for 3 and 5 days on SCGlu plates, respectively. Diameters were evaluated by processing the photos with Metamorph Imaging (mean±SEM, n = 2).
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pone-0004592-g002: An oxa1 deletion does not influence the strains growth rate.(A) Growth curves of an oxa1 deletion strain and the corresponding wild-type strain. Experiment was performed in triplicate. The y-axis is scaled logarithmically. (B) Size of isolated colonies of the indicated strains grown for 3 and 5 days on SCGlu plates, respectively. Diameters were evaluated by processing the photos with Metamorph Imaging (mean±SEM, n = 2).

Mentions: To exclude rho0 strain specific effects not accounting for respiration deficiencies, two other respiration impaired strains were investigated. Single gene deletion strains of both, MGM1 (homolog to human OPA1) - a GTPase located in the mitochondrial intermembrane space [24] - and OXA1 (an insertase of the inner mitochondrial membrane – highly conserved from prokaryotes to mammals [25], [26]) behaved like the (wild-type) rho0 strain. After 3 and 5 days, mgm1 as well as oxa1 deleted cells retrieved from the whole colony (3 days) or the central region (5 days), and thus mainly older cells, showed significantly increased survival (Fig. 1A) as well as inhibition of ROS generation compared to samples of the wild-type strain (Fig. 1B). Of note, unlike other respiration deficient mutant strains (including rho0 and Δmgm1) the Δoxa1 strain showed same growth rates as the wild-type strain in liquid cultures and during colony growth, respectively (Fig. 2A and B).


The Warburg effect suppresses oxidative stress induced apoptosis in a yeast model for cancer.

Ruckenstuhl C, Büttner S, Carmona-Gutierrez D, Eisenberg T, Kroemer G, Sigrist SJ, Fröhlich KU, Madeo F - PLoS ONE (2009)

An oxa1 deletion does not influence the strains growth rate.(A) Growth curves of an oxa1 deletion strain and the corresponding wild-type strain. Experiment was performed in triplicate. The y-axis is scaled logarithmically. (B) Size of isolated colonies of the indicated strains grown for 3 and 5 days on SCGlu plates, respectively. Diameters were evaluated by processing the photos with Metamorph Imaging (mean±SEM, n = 2).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2643009&req=5

pone-0004592-g002: An oxa1 deletion does not influence the strains growth rate.(A) Growth curves of an oxa1 deletion strain and the corresponding wild-type strain. Experiment was performed in triplicate. The y-axis is scaled logarithmically. (B) Size of isolated colonies of the indicated strains grown for 3 and 5 days on SCGlu plates, respectively. Diameters were evaluated by processing the photos with Metamorph Imaging (mean±SEM, n = 2).
Mentions: To exclude rho0 strain specific effects not accounting for respiration deficiencies, two other respiration impaired strains were investigated. Single gene deletion strains of both, MGM1 (homolog to human OPA1) - a GTPase located in the mitochondrial intermembrane space [24] - and OXA1 (an insertase of the inner mitochondrial membrane – highly conserved from prokaryotes to mammals [25], [26]) behaved like the (wild-type) rho0 strain. After 3 and 5 days, mgm1 as well as oxa1 deleted cells retrieved from the whole colony (3 days) or the central region (5 days), and thus mainly older cells, showed significantly increased survival (Fig. 1A) as well as inhibition of ROS generation compared to samples of the wild-type strain (Fig. 1B). Of note, unlike other respiration deficient mutant strains (including rho0 and Δmgm1) the Δoxa1 strain showed same growth rates as the wild-type strain in liquid cultures and during colony growth, respectively (Fig. 2A and B).

Bottom Line: Research has mainly focused on a possible connection between increased glycolysis and tumor development whereas decreased respiration has largely been left unattended.Therefore, a causal relation between decreased respiration and tumorigenesis has not been demonstrated.In contrast, enhancement of respiration triggered cell death.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Biosciences, University of Graz, Graz, Austria.

ABSTRACT

Background: Otto Warburg observed that cancer cells are often characterized by intense glycolysis in the presence of oxygen and a concomitant decrease in mitochondrial respiration. Research has mainly focused on a possible connection between increased glycolysis and tumor development whereas decreased respiration has largely been left unattended. Therefore, a causal relation between decreased respiration and tumorigenesis has not been demonstrated.

Methodology/principal findings: For this purpose, colonies of Saccharomyces cerevisiae, which is suitable for manipulation of mitochondrial respiration and shows mitochondria-mediated cell death, were used as a model. Repression of respiration as well as ROS-scavenging via glutathione inhibited apoptosis and conferred a survival advantage during seeding and early development of this fast proliferating solid cell population. In contrast, enhancement of respiration triggered cell death.

Conclusion/significance: Thus, the Warburg effect might directly contribute to the initiation of cancer formation--not only by enhanced glycolysis--but also via decreased respiration in the presence of oxygen, which suppresses apoptosis.

Show MeSH
Related in: MedlinePlus