Figure 7.

Mutant IDH1 sensitizes cells to inhibition of oxidative mitochondrial metabolism. Left, under normal growth conditions, glucose is metabolized oxidatively in the mitochondria, and AcCoA and lipids are derived mainly from glucose carbons. Middle, in IDH1 WT cells, inhibition of oxidative mitochondrial metabolism (induced by growth in hypoxia or pharmacologic inhibitors of the ETC) limits glucose flux to the mitochondria, and cells instead rely on reductive glutamine metabolism via IDH1 to provide carbons for AcCoA generation and lipid synthesis. Right, when oxidative mitochondrial metabolism is inhibited, cells with a mutant IDH1 allele are unable to fully induce reductive glutamine metabolism and are thus compromised for AcCoA and lipid production, leading to decreased cell growth.