Figure 5.

TFAM knockdown down‐regulates p53/TIGAR signal pathway. A, Western blotting analysis of p53 levels in control and TFAM knockdown MCF7, U‐2 OS and Hep G2 cells; B, The protein levels of p53 and TIGAR in control and TFAM knockdown U‐2 OS cells after radiation and nutlin‐3 treatment; C, The DNA double‐strand breaks levels in control and TFAM knockdown U‐2 OS cells after radiation and nutlin‐3 treatment; D, Analysis of the binding between p53 and MDM2 in control and TFAM knockdown U‐2 OS and MCF7 cells by immunoprecipitation and immunoblotting analysis. *, ** and *** represents P < 0.05, 0.01 and 0.001 respectively; E, Schematic illustration of the proposed model. TFAM knockdown enhanced the interaction between p53 and MDM2, resulting in the down‐regulation of p53 and lowered expression of TIGAR. This further increased the accumulation of mitochondrial superoxide ROS and induced the DNA damage. And therefore, after exposure to irradiation, DNA damages in irradiated cells will be exaggerated