This study demonstrates that mitochondrial autophagy is induced by hypoxia and is dependent on the expression of BNIP3, Beclin-1, and Atg5. In cells exposed to prolonged hypoxia, mitochondrial autophagy is an adaptive metabolic response necessary to prevent increased levels of reactive oxygen species (ROS) and cell death. The survival of metazoan organisms depends on their ability to efficiently generate energy through mitochondrial oxidative phosphorylation, but this process also generates ROS, which can lead to cell dysfunction or death. Hypoxia-inducible factor 1 (HIF-1) plays a key role in regulating oxygen homeostasis by controlling the transcription of genes involved in erythropoiesis, angiogenesis, and energy metabolism. The study shows that HIF-1 regulates mitochondrial mass and respiration under normal physiological conditions and that prolonged exposure to hypoxia results in a HIF-1-dependent reduction in mitochondrial mass and respiration. The induction of mitochondrial autophagy, in concert with inhibition of mitochondrial biogenesis, represents a critical adaptive mechanism to maintain oxygen homeostasis under hypoxic conditions. The functional significance of this autophagy is demonstrated by its protective effect on cell survival under hypoxic conditions, as loss of BNIP3, Beclin-1, or Atg5 leads to increased ROS levels and cell death. These findings highlight the importance of mitochondrial autophagy in maintaining energy and redox homeostasis under hypoxic conditions.This study demonstrates that mitochondrial autophagy is induced by hypoxia and is dependent on the expression of BNIP3, Beclin-1, and Atg5. In cells exposed to prolonged hypoxia, mitochondrial autophagy is an adaptive metabolic response necessary to prevent increased levels of reactive oxygen species (ROS) and cell death. The survival of metazoan organisms depends on their ability to efficiently generate energy through mitochondrial oxidative phosphorylation, but this process also generates ROS, which can lead to cell dysfunction or death. Hypoxia-inducible factor 1 (HIF-1) plays a key role in regulating oxygen homeostasis by controlling the transcription of genes involved in erythropoiesis, angiogenesis, and energy metabolism. The study shows that HIF-1 regulates mitochondrial mass and respiration under normal physiological conditions and that prolonged exposure to hypoxia results in a HIF-1-dependent reduction in mitochondrial mass and respiration. The induction of mitochondrial autophagy, in concert with inhibition of mitochondrial biogenesis, represents a critical adaptive mechanism to maintain oxygen homeostasis under hypoxic conditions. The functional significance of this autophagy is demonstrated by its protective effect on cell survival under hypoxic conditions, as loss of BNIP3, Beclin-1, or Atg5 leads to increased ROS levels and cell death. These findings highlight the importance of mitochondrial autophagy in maintaining energy and redox homeostasis under hypoxic conditions.