The Warburg Effect in a Metazoan Capable of Anaerobic Mitochondrial Metabolism

AbstractThe Warburg effect-aerobic glycolysis, diminished oxygen uptake, and lactate secretion-has been characterized in proliferative mammalian cells and in some cancers. Lactate formation remains puzzling, variously attributed to reoxidizing NADH or activating the cell cycle. Forming lactate provides the only anaerobic pathway available to mammalian cells but not for most eukaryotes or metazoans. With the purely mitotic polyp stage of a colonial marine hydroid, Eirene sp., differential feeding was used to create rapidly and slowly proliferating colonies of a genetically identical clone. The former were fed to excess three times per week, the latter once per week. Under aerobic conditions, assays using gas chromatography/mass spectrometry show that colonies of both treatments produce short-chain fatty acids, indicating end products of anaerobic mitochondrial metabolism and thus providing an alternative pathway to reoxidize NADH. After 1 h of incubation in fully aerated seawater, the concentration of acetate, propionate, and butyrate was higher in the medium than in the tissue of the colonies, suggesting that these are waste products. Colorimetric assays showed that colonies of both treatments nevertheless produced lactate. Further, the rapidly proliferating colonies produced significantly more. Eirene sp. thus carries out anaerobic mitochondrial metabolism, but this apparently has no effect on lactate production. Since earlier data show that the proliferative colonies exhibit diminished oxygen uptake, anaerobic mitochondrial metabolism appears to have little impact on the Warburg effect. This contrasts with the expectation from the literature that an alternative pathway to reoxidize NADH will abolish lactate production.