Turning the Oxygen and Vitamin Dials

Abstract

Oxygen deprivation (hypoxia) and excess (hyperoxia) are both toxic to humans. Oxygen deprivation contributes to 3 of the 5 leading causes of mortality in developed nations -- heart attack, stroke, and respiratory failure. On the other hand, hyperoxia is toxic to nearly all organisms and contributes to the pathology of ischemia-reperfusion injury, mitochondrial disease and hyperoxic lung injury. However, the molecular mechanisms underlying hypoxia and hyperoxia toxicity remain unknown. By deciphering these mechanisms, we strive to nominate novel therapeutic candidates. Our recent work highlights such mechanisms of hyperoxia toxicity and the cycle of damage caused by destabilization of specific iron-containing protein complexes. While small molecules and biologics are the most common forms of therapy, we believe we have uncovered a new mode of treating metabolic disorders. We now hope to extend our findings to additional inborn errors of metabolism, as well as more common metabolic disorders, including aging and age-associated damage.