Alternatively, in hypoxic conditions, in which cancer cells rewire many mitochondrial processes [43], α-KG, produced by hGDH, [44] might be reductively carboxylated to isocitrate by mitochondrial isocitrate dehydrogenase (IDH2) in a reverse mode of TCA cycle function, fostering citrate synthesis for fatty acid biosynthesis This citrate synthesis requires a high mitochondrial NADPH/NADP+ ratio ensured by GDH activity and mitochondrial nicotinamide nucleotide transhydrogenase that synthesizes NADPH from NADH. Here, IDH2 is linked to cancer.