Regulation of autophagy in oxygen-dependent cellular stress

Stefan W. Ryter, Augustine M.K. Choi

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Oxidative stress caused by supraphysiological production of reactive oxygen species (ROS), can cause cellular injury associated with protein and lipid oxidation, DNA damage, and mitochondrial dysfunction. The cellular responses triggered by oxidative stress include the altered regulation of signaling pathways that culminate in the regulation of cell survival or cell death pathways. Recent studies suggest that autophagy, a cellular homeostatic process that governs the turnover of damaged organelles and proteins, may represent a general cellular and tissue response to oxidative stress. The autophagic pathway involves the encapsulation of substrates in doublemembraned vesicles, which are subsequently delivered to the lysosome for enzymatic degradation and recycling of metabolic precursors. Autophagy may play multifunctional roles in cellular adaptation to stress, by maintaining mitochondrial integrity, and removing damaged proteins. Additionally, autophagy may play important roles in the regulation of inflammation and immune function. Modulation of the autophagic pathway has been reported in cell culture models of oxidative stress, including altered states of oxygen tension (i.e., hypoxia, hyperoxia), and exposure to oxidants. Furthermore, proteins that regulate autophagy may be subject to redox regulation. The heme oxygenase- 1 (HO)-1 enzyme system may have a role in the regulation of autophagy. Recent studies suggest that carbon monoxide (CO), a reaction product of HO activity which can alter mitochondrial function, may induce autophagy in cultured epithelial cells. In conclusion, current research suggests a central role for autophagy as a mammalian oxidative stress response and its interrelationship to other stress defense systems.

Original languageEnglish (US)
Pages (from-to)2747-2756
Number of pages10
JournalCurrent Pharmaceutical Design
Volume19
Issue number15
DOIs
StatePublished - 2013

Keywords

  • Autophagy
  • Carbon monoxide
  • Heme oxygenase-1
  • Hyperoxia
  • Hypoxia
  • Mitochondria
  • Oxidative stress
  • Reactive oxygen species

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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