Cellular adaptation to oxygen deficiency beyond the Nobel award

Abstract

Understanding the cellular adaptation to oxygen deficiency -hypoxia- has a profound impact on our knowledge of the pathogenesis of several diseases. The elucidation of the molecular machinery that regulates response to hypoxia has been awarded the Nobel Prize in Physiology or Medicine. The enrichment of Earth’s atmosphere in molecular oxygen (O2) by photosynthesis over the past billion years determined the appearance of sophisticated multicellular organisms, which led to the evolution of mammals and mankind. Our cells, in particular neurons and muscle, need O2 to extract the energy necessary to maintain essential vital functions from nutrients. This O2 is obtained from ambient air and transported to cells. Reduced O2 levels—or hypoxia—can happen systemically, due either to decreased atmospheric O2 or impairment of gas exchange in the lungs or locally in tissues and cells. Hypoxia, even if lasting only a few minutes, can produce irreversible cellular damage, as occurs in heart attacks or strokes. Therefore, both cellular adaptive biochemical responses to sus- tained hypoxia (hours or days) and organismal reflexes to acutely (in seconds) adapt to systemic hypoxia have evolved to compensate for the lack of O2 in mammals1. However, how cells/organisms detect O2 deficiency and the underlying molecular mechanisms are questions that have begun to be clarified in the past three decades. These advances have been recognized in 2019 with the Nobel Prize in Physiology or Medicine awarded to William G. Kaelin, Peter J. Ratcliffe, and Gregg L. Semenza