Ruckenstuhl Christoph, Büttner Sabrina, Carmona-Gutierrez Didac, Eisenberg Tobias, Kroemer Guido, Sigrist Stephan J, Fröhlich Kai-Uwe, Madeo Frank
Institute of Molecular Biosciences, University of Graz, Graz, Austria.
PLoS One. 2009;4(2):e4592. doi: 10.1371/journal.pone.0004592. Epub 2009 Feb 25.
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.
奥托·瓦尔堡观察到癌细胞的特征通常是在有氧存在的情况下进行强烈的糖酵解，同时线粒体呼吸作用相应减弱。研究主要集中在糖酵解增加与肿瘤发展之间可能存在的联系，而呼吸作用减弱在很大程度上被忽视了。因此，呼吸作用减弱与肿瘤发生之间的因果关系尚未得到证实。
方法/主要发现：为此，酿酒酵母菌落被用作模型，它适合用于操纵线粒体呼吸作用，并表现出线粒体介导的细胞死亡。呼吸作用的抑制以及通过谷胱甘肽清除活性氧抑制了细胞凋亡，并在这种快速增殖的实体细胞群体的接种和早期发育过程中赋予了生存优势。相反，呼吸作用的增强引发细胞死亡。
结论/意义：因此，瓦尔堡效应可能直接促成癌症形成的起始——不仅通过增强糖酵解——还通过在有氧存在的情况下呼吸作用减弱，从而抑制细胞凋亡。
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