Figure 6

Schema outlining the proposed pathway by which SIRT4 regulates proliferation. It is proposed that under nutrient rich conditions mTORC1 inhibits CREB2, decreasing the expression of SIRT4. When SIRT4 activity is decreased, which is observed in the Sirt4 knockout mice, and what might be expected with increasing age, the glutamate/αketoglutarate and TCA cycles are dysregulated. As such, it is suggested that this plays a role, at least in some part, in the tumor-permissive phenotype in mice lacking Sirt4.