The downstream signaling triggered by HIF activation is a key molecular mechanism for cells to adapt to hypoxia.459,460 Chiu et al. found that the HIF1 and Notch signaling pathways interact to control mitochondrial biogenesis in cancer cells and maintain redox balance.461 Specifically, HIF1 directly binds to the hypoxia response element of HEY1 in the Notch signaling pathway, activating the transcription of HEY1 in HCC. Here, HEY1 is linked to hepatocellular carcinoma.