Figure 6.

NAD metabolism in cancer cells. Cancer cells rely on increased glycolysis rates for energy production and regenerate NAD⁺ by converting accumulating pyruvate into lactate to maintain glycolysis. Excess lactate accumulation in tumor cells increases the level of NADH relative to NAD and perturbs the NAD/NADH balance in cells [204]. In contrast, SIRT1 acts as an inactivator of HIFα and prevents its nuclear translocation. SIRT6 acts as a corepressor of HIFα to prevent the transcriptional process, and mitochondrial-localized SIRT3 suppresses ROS production.