Fig. 2

Hypoxic HIFα-Dependent Glucose Metabolic Reprogramming. Metabolic pathways illustrating HIFα transcriptional targets under hypoxia in tumor cells. Blue boxes, known HIFα targets. HIFα induces the expression of GLUT1, GLUT3, HK1/2 and LDHA, to increase glucose uptake and lactate formation. HIFα also induces the expression of PDK1, which then negatively regulates the entry of pyruvate to the TCA cycle. In addition, under hypoxic conditions, HIF-1 reduces the activity and respiration of complex I by inducing NDUFA4L2, and induces the expression of several microRNAs (miRNA) including miR-210, which can inhibit the assembly of ETC complex, thereby reducing the activity of ETC.