Mitochondrial autophagy: life and breath of the cell.
Homeostatic responses to reduced O(2) availability are regulated by the transcriptional activator hypoxia-inducible factor 1 (HIF-1) in all metazoan species. An essential adaptation to sustained hypoxia is an active repression of mitochondrial respiration. In mouse embryo fibroblasts, HIF-1 induces expression of BNIP3, which triggers selective mitochondrial autophagy. When exposed to hypoxia, HIF-1-deficient cells do not induce BNIP3 or autophagy, do not decrease mitochondrial mass or downregulate respiration, and die within 72 hours due to toxic levels of reactive oxygen species. These studies indicate that mitochondrial autophagy represents an adaptive metabolic response to hypoxia that is necessary to maintain redox homeostasis and cell survival.
Semenza
Gregg L
GL
Vascular Program, Institute for Cell Engineering, Department of Pediatrics, McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. gsemenza@jhmi.edu
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D019069:Cell Respiration / Q000502:physiology*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D000860:Hypoxia; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism
C508686:BNip3 protein, mouse; D051793:Hypoxia-Inducible Factor 1; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D010100:Oxygen