In LECs, OXPHOS is the major source for ATP production. However, TLECs shifted from OXPHOS to glycolysis for the production of energy (Warburg effect). The increased level of ROS production in TLECs has been shown to inhibit prolyl hydroxylase enzyme (PHD) activity, thus preventing HIF-1α proteasomal degradation. Consequently, HIF-1α is stabilized and translocates to the nucleus, where it dimerizes with HIF-1β, initiating the transcription of HIF-1 responsiveness genes including most of the glycolytic enzymes that promote glycolysis in TLECs. However, in response to different microenvironments, hypoxia conditions, and the sequence of oncogenic activation and tumor suppressor gene inactivation, TLECs may express upregulation of OXPHOS components.