CYCS and cancer: Our work revealed that, at the membrane of mitochondrial, the hierarchical involvement of Bim, VDAC1, and ATF2 break the hexokinase-1 (HK1) and voltage-dependent anion channel-1 (VDAC1) complexes, thereby enhancing mitochondrial permeability and releasing cytochrome c. The exploration of the mechanisms for ATF2 mitochondrial localization offers a theoretical basis to guide cancer cells to apoptosis.