The fundamental question of how cells sense oxygen has implications for embryogenesis, cancer, stroke, diabetes, and other ischemic diseases. Clearly, this is important work, and many researchers have taken up the task. Yet, despite the publication of hundreds of papers on this subject, no clear consensus exists regarding what the cellular oxygen sensor is, or even the number of sensing mechanisms there might be.
The literature presents several possibilities. One theory holds that a heme-containing protein undergoes a conformational change when bound to oxygen, thereby "sensing" oxygen. Two other related hypotheses center around reactive oxygen species (ROS), which are highly unstable, highly reactive superoxides. One ROS theory holds that, as oxygen levels decrease, so do ROS levels. The second theory hypothesizes the opposite, countering that as oxygen levels decrease, ROS levels increase. Each theory has its supporters and detractors, who have published many articles to advance their particular vantage point.1
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