Autophagic proteins: new facets of the oxygen paradox. Academic Article uri icon

Overview

MeSH

  • Antigens, CD95
  • Apoptosis
  • Death Domain Receptor Signaling Adaptor Proteins
  • Epithelial Cells
  • Humans
  • Microtubule-Associated Proteins
  • Reactive Oxygen Species
  • Signal Transduction

MeSH Major

  • Autophagy
  • Membrane Proteins
  • Models, Biological
  • Oxygen

abstract

  • Oxygen (O 2), 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 O 2 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 O 2 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 O 2 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.

publication date

  • March 2012

has subject area

  • Antigens, CD95
  • Apoptosis
  • Autophagy
  • Death Domain Receptor Signaling Adaptor Proteins
  • Epithelial Cells
  • Humans
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Models, Biological
  • Oxygen
  • Reactive Oxygen Species
  • Signal Transduction

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3337844

Digital Object Identifier (DOI)

  • 10.4161/auto.19258

PubMed ID

  • 22302001

Additional Document Info

start page

  • 426

end page

  • 428

volume

  • 8

number

  • 3