title: Signaling pathways and mechanisms of hypoxia-induced autophagy in the animal cells.
abstract: Hypoxia occurs in a series of supraphysiological circumstances, for instance, sleep disorders, myocardial infarction and cerebral stroke, that can induce a systematic inflammatory response. Such a response may then lead to a widespread dysfunction and cell injury. Autophagy, a cellular homeostatic process that governs the turnover of damaged organelles and proteins, can be triggered by multiple forms of extra- and intracellular stress, for example, hypoxia, nutrient deprivation and reactive oxygen specie. Central to this process is the formation of double-membrane vesicles, thereby autophagosomes sequester portions of cytosol and deliver them to the lysosomes for a breakdown. In recent years, several distinct oxygen-sensing pathways that regulate the cellular response to autophagy have been defined. For instance, hypoxia influences autophagy in part through the activation of the hypoxia-inducible factor (HIF)-dependent pathways. In chronic and moderate hypoxia, autophagy plays a protective role by mediating the removal of the damaged organelles and protein. Moreover, three additional oxygen-sensitive signaling pathways are also associated with the activation of autophagy. These include mammalian target of rapamycin (mTOR) kinase, unfolded protein response (UPR)- and PKCδ-JNK1-dependent pathways. Contrary to the protective effects of autophagy, during rapid and severe oxygen fluctuations, autophagy may be detrimental and induce cell death. In this review, we highlight a serious of recent advances on how autophagy is regulated at the molecular level and on final consequences of cell under different hypoxic environment.
authors: Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, Tianjin, China.
authors: Yungyun
authors: Y
authors: Fang
authors: Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, Tianjin, China.
authors: Jin
authors: J
authors: Tan
authors: Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, Tianjin, China.
authors: Qiang
authors: Q
authors: Zhang
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D058570:TOR Serine-Threonine Kinases; D011493:Protein Kinase C; D048670:MAP Kinase Kinase 4
keywords: HIF; PKCδ-JNK1; UPR; autophagy; hypoxia; mTOR