Balancing the generation and elimination of reactive oxygen species

Fossil records suggest that bacteria developed the ability to photosynthesize ≈3,500 million years ago (mya), initiating a very slow accumulation of atmospheric oxygen (1). Recent geochemical models suggest that atmospheric oxygen did not accumulate to levels conducive for aerobic life until 500–1,000 mya (2, 3). The oxygenation of Earth's atmosphere resulted in the emergence of aerobic organisms followed by a great diversification of biological species and the eventual evolution of humans. Although oxygen is thought to have been responsible for the expansion of life on Earth, there are two sides to this molecule: life giving and life taking. Oxygen in the air we breathe is a relatively nonreactive chemical (4). However, when oxygen is exposed to high-energy or electron-transferring chemical reactions, it can be converted to various highly reactive chemical forms (Fig. 1) collectively designated “reactive oxygen species” (ROS; ref. 5). ROS are toxic to biological organisms because they oxidize lipids, proteins, DNA, and carbohydrates, resulting in the breakdown of normal cellular, membrane, and reproductive functions. Ultimately, toxic levels of ROS cause a chain reaction of cellular oxidation, resulting in disease and lethality (5–7). ROS are unavoidable byproducts of biochemical pathways, such as glycolysis and photosynthesis, that are central to energy production and storage …