Mitochondria in cancer: not just innocent bystanders.
The first half of the 20th century produced substantial breakthroughs in bioenergetics and mitochondria research. During that time, Otto Warburg observed abnormally high glycolysis and lactate production in oxygenated cancer cells, leading him to suggest that defects in mitochondrial functions are at the heart of malignant cell transformation. Warburg's hypothesis profoundly influenced the present perception of cancer metabolism, positioning what is termed aerobic glycolysis in the mainstream of clinical oncology. While some of his ideas stood the test of time, they also frequently generated misconceptions regarding the biochemical mechanisms of cell transformation. This review examines experimental evidence which supports or refutes the Warburg effect and discusses the possible advantages conferred on cancer cells by 'metabolic transformation'.
Frezza
Christian
C
Cancer Research UK, The Beatson Institute for Cancer Research, Glasgow, Scotland, United Kingdom.
Gottlieb
Eyal
E
D000818:Animals; D019069:Cell Respiration / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D006019:Glycolysis / Q000502:physiology*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D013385:Succinate Dehydrogenase / Q000378:metabolism
D051793:Hypoxia-Inducible Factor 1; D013385:Succinate Dehydrogenase