Autophagy is a process by which cytoplasmic organelles can be catabolized, either to remove defective structures or as a means of providing macromolecules for energy generation under conditions of nutrient starvation. In this study, we demonstrate: that mitochondrial autophagy is induced by hypoxia; that this process requires the HIF-1-inducible expression of BNIP3 and the constitutive expression of Beclin-1 and Atg5; and that in cells subjected to prolonged hypoxia, mitochondrial autophagy is an adaptive metabolic response, which is necessary to prevent increased levels of reactive oxygen species and cell death.