The article discusses the role of Hypoxia-inducible factors (HIFs) in cellular responses to hypoxic stress. HIFs are transcription factors that play a crucial role in regulating gene expression in response to low oxygen levels. The article highlights the regulation of HIFs by various factors, including prolyl hydroxylases (PHDs), Factor Inhibiting HIF-1α (FIH1), sirtuins, and metabolites. It also explores the functions of HIFs in different cellular and tissue stress responses, such as metabolism, redox homeostasis, and angiogenesis. The article further delves into the complex regulation of HIFα subunits, the role of HIFs in cancer, inflammation, and endothelial cell function. Additionally, it examines the impact of HIFs on lipid metabolism, metastasis, and tumor angiogenesis. The article concludes by discussing the potential of targeting HIFs in therapeutic strategies for various diseases.The article discusses the role of Hypoxia-inducible factors (HIFs) in cellular responses to hypoxic stress. HIFs are transcription factors that play a crucial role in regulating gene expression in response to low oxygen levels. The article highlights the regulation of HIFs by various factors, including prolyl hydroxylases (PHDs), Factor Inhibiting HIF-1α (FIH1), sirtuins, and metabolites. It also explores the functions of HIFs in different cellular and tissue stress responses, such as metabolism, redox homeostasis, and angiogenesis. The article further delves into the complex regulation of HIFα subunits, the role of HIFs in cancer, inflammation, and endothelial cell function. Additionally, it examines the impact of HIFs on lipid metabolism, metastasis, and tumor angiogenesis. The article concludes by discussing the potential of targeting HIFs in therapeutic strategies for various diseases.