Authors: Yang Jin, Akihiko Tanaka, Augustine M.K. Choi and Stefan W. Ryter

Yang Jin

Pulmonary and Critical Care Medicine; Brigham and Women's Hospital; Harvard Medical School; Boston, MA USA

Akihiko Tanaka

Department of Internal Medicine; Division of Allergy and Respiratory Medicine; Showa University; Tokyo, Japan

Augustine M.K. Choi

Pulmonary and Critical Care Medicine; Brigham and Women's Hospital; Harvard Medical School; Boston, MA USA

Stefan W. Ryter

Corresponding author: Sryter@partners.org
Pulmonary and Critical Care Medicine; Brigham and Women's Hospital; Harvard Medical School; Boston, MA USA

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Abstract:

Oxygen (O₂), while essential for aerobic life, can also cause metabolic toxicity through the excess generation of reactive oxygen species (ROS). Pathological changes in ROS production can originate through the partial reduction of O₂ during mitochondrial electron transport, as well as from enzymatic sources. This phenomenon, termed the oxygen paradox, has been implicated in aging and disease, and is especially evident in critical care medicine. Whereas high O₂ concentrations are utilized as a life-sustaining therapeutic for respiratory insufficiency, they in turn can cause acute lung injury. Alveolar epithelial cells represent a primary target of hyperoxia-induced lung injury. Recent studies have indicated that epithelial cells exposed to high O₂ concentrations die by apoptosis, or necrosis, and can also exhibit mixed-phenotypes of cell death (aponecrosis). Autophagy, a cellular homeostatic process responsible for the lysosomal turnover of organelles and proteins, has been implicated as a general response to oxidative stress in cells and tissues. This evolutionarily conserved process is finely regulated by a complex interplay of protein factors. During autophagy, senescent organelles and cellular proteins are sequestered in autophagic vacuoles (autophagosomes) and subsequently targeted to the lysosome, where they are degraded by lysosomal hydrolases, and the breakdown products released for reutilization in anabolic pathways. Autophagy has been implicated as a cell survival mechanism during nutrient-deficiency states, and more generally, as a determinant of cell fate. However, the mechanisms by which autophagy and/or autophagic proteins potentially interact with and/or regulate cell death pathways during high oxygen stress, remain only partially understood.

Autophagic Punctum to:
A Tanaka, Y Jin, SJ Lee, M Zhang, HP Kim, DB Stolz, SW Ryter, AM Choi. Hyperoxia-induced LC3B interacts with the Fas apoptotic pathway in epithelial cell death. Am J Respir Cell Mol Biol 2012; 46: 507-14
PMID: 22095627 DOI: 10.1165/rcmb.2009-0415OC