Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. This study demonstrates that hypoxia induces mitochondrial autophagy, which requires HIF-1-dependent expression of BNIP3 and constitutive expression of Beclin-1 and Atg5. In prolonged hypoxia, mitochondrial autophagy is an adaptive response that prevents increased reactive oxygen species (ROS) and cell death. Hypoxia-inducible factor 1 (HIF-1) regulates oxygen homeostasis by controlling gene expression, including those involved in energy and redox homeostasis. HIF-1 coordinates a switch in cytochrome c oxidase subunit utilization, activates PDK1 to shunt pyruvate away from mitochondria, and increases glucose flux to lactate. It also represses mitochondrial biogenesis and respiration. Mitochondrial autophagy is a critical adaptive mechanism under hypoxia, involving BNIP3, Beclin-1, and Atg5. BNIP3 induces autophagy by disrupting Beclin-1-Bcl2 interactions, leading to increased free Beclin-1 and autophagy. HIF-1-dependent BNIP3 expression is essential for mitochondrial autophagy, which helps maintain redox homeostasis and cell survival under hypoxia. The study shows that mitochondrial autophagy is required for cell survival under prolonged hypoxia, as its inhibition leads to increased ROS and cell death. These findings highlight the role of autophagy in maintaining cellular function under hypoxic conditions.Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. This study demonstrates that hypoxia induces mitochondrial autophagy, which requires HIF-1-dependent expression of BNIP3 and constitutive expression of Beclin-1 and Atg5. In prolonged hypoxia, mitochondrial autophagy is an adaptive response that prevents increased reactive oxygen species (ROS) and cell death. Hypoxia-inducible factor 1 (HIF-1) regulates oxygen homeostasis by controlling gene expression, including those involved in energy and redox homeostasis. HIF-1 coordinates a switch in cytochrome c oxidase subunit utilization, activates PDK1 to shunt pyruvate away from mitochondria, and increases glucose flux to lactate. It also represses mitochondrial biogenesis and respiration. Mitochondrial autophagy is a critical adaptive mechanism under hypoxia, involving BNIP3, Beclin-1, and Atg5. BNIP3 induces autophagy by disrupting Beclin-1-Bcl2 interactions, leading to increased free Beclin-1 and autophagy. HIF-1-dependent BNIP3 expression is essential for mitochondrial autophagy, which helps maintain redox homeostasis and cell survival under hypoxia. The study shows that mitochondrial autophagy is required for cell survival under prolonged hypoxia, as its inhibition leads to increased ROS and cell death. These findings highlight the role of autophagy in maintaining cellular function under hypoxic conditions.