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


RESULTS
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.


CONCLUSIONS
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.
Ruckenstuhl
Christoph
C
Institute of Molecular Biosciences, University of Graz, Graz, Austria.
Büttner
Sabrina
S
Carmona-Gutierrez
Didac
D
Eisenberg
Tobias
T
Kroemer
Guido
G
Sigrist
Stephan J
SJ
Fröhlich
Kai-Uwe
KU
Madeo
Frank
F
D016923:Cell Death; D049109:Cell Proliferation; D019069:Cell Respiration; D002470:Cell Survival; D004734:Energy Metabolism; D005978:Glutathione / Q000494:pharmacology; D006019:Glycolysis; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism
D005978:Glutathione; D010100:Oxygen