Hypoxia activation of mitophagy and its role in disease pathogenesis

• Published in: Antioxidants & redox signaling Vol. 22; no. 12; p. 1032
• Main Authors: Wu, Hao, Chen, Quan
• Format: Journal Article
• Language: English
• Published: United States 20.04.2015
• Subjects: Apoptosis Regulatory Proteins - metabolism; Autophagy; Cell Hypoxia; Humans; Metabolic Diseases - metabolism; Mitochondrial Degradation; Neoplasms - metabolism; Neurodegenerative Diseases - metabolism
• ISSN: 1557-7716
• DOI: 10.1089/ars.2014.6204

Mitochondria utilize most of the oxygen to produce adenosine triphosphate via electron transfer coupled with oxidative phosphorylation. Hypoxia undoubtedly induces reduced energy production via decreased mitochondrial metabolic activity or altered hypoxia-inducible factor-1- and peroxisome proliferator-activated receptor gamma coactivator 1-dependent mitochondrial biogenesis. Hypoxia may also activate mitophagy to selectively remove damaged or unwanted mitochondria for both mitochondrial quantity and quality control. Increasing evidence has shown that the accumulation of damaged mitochondria is a characteristic of aging and aging-related diseases, such as metabolic disorder, cancer, and neurodegenerative disease. Both receptor-dependent and PTEN-induced putative kinase 1-PARKIN-dependent mitophagy have been described. Mitophagy receptors include Atg32 in yeast, as well as NIX/BNIP3L, B-cell lymphoma 2/adenovirus E1B 19-kDa-interacting protein 3 and FUN14 domain containing 1 in mammals. In response to hypoxia or mitochondrial oxidative stress, receptor-mediated mitophagy was found to be activated via both transcriptional and post-translational modification. To date, the molecular mechanisms by which hypoxia triggers mitophagy and by which mitophagy contributes to the pathogenesis of aging-related diseases remain to be explored. An improved understanding of the regulation of mitochondrial quality may provide a strategy for treating aging-related diseases by targeting mitochondria and mitophagy pathways.