Succination-mediated translocation of PKM2 to mitochondria under glucose starvation conditions plays a role in the cell’s switch from a proliferative mode to a survival mode, and vice versa. Mitochondrial PKM2 inhibits ubiquitination-mediated degradation of VDAC3 and increases mitochondrial permeability, producing more ATP to maintain cell survival under nutrient depletion. In human colorectal cancer, the upregulation of mitochondrial PKM2 is positively correlated with the upregulation of VDAC3. Here, VDAC3 is linked to colorectal cancer.