Pyruvate dehydrogenase activity is required for optimal growth under lipid deficient conditions

Background Otto Warburg’s observation that tumor cells have increased rates of glucose uptake and lactate secretion in comparison to normal cells spawned his notion that tumors have dysfunctional mitochondria. However, in addition to metabolizing glucose to lactate, tumors in vivo exhibit mitochondrial glucose oxidation, indicating activity of pyruvate dehydrognase (PDH), which gates entry of glucose derived carbon into the tricarboxylic acid (TCA) cycle [1]. Here we establish a model wherein we suppress PDH activity using RNAi, thus abrogating the flux of glucose derived carbon into the TCA cycle and ultimately lipids, and determine the extent to which PDH activity and oxidative metabolism of glucose are required for the growth of cancer cells.