PDK1 and hepatocellular carcinoma: Following the example of PDK1, another mechanism involved in the OXPHOS down-regulation and tumor aggressiveness under hypoxia (1% O2) is the modification of mitochondrial mass and morphology by PINK1 down-regulation through HIF-1-mediated NOTCH signaling activation in hepatocellular carcinoma cells, a cancer type highly resistant to radiotherapy (32).