No abstract

Mitochondrial superoxide dismutase (MnSOD) neutralizes the highly reactive superoxide radical (O2·−), the first member in a plethora of mitochondrial reactive oxygen species (ROS). Over the past decades, research has extended the prevailing view of mitochondrion well beyond the generation of cellular energy to include its importance in cell survival and cell death. In the normal state of a cell, endogenous antioxidant enzyme systems maintain the level of reactive oxygen species generated by the mitochondrial respiratory chain. Mammalian mitochondria are important to the production of reactive oxygen species, which underlie oxidative damage in many pathological conditions and contribute to retrograde redox signaling from the organelle to the cytosol and nucleus. Mitochondria are further implicated in various metabolic and aging-related diseases that are now postulated to be caused by misregulation of physiological systems rather than pure accumulation of oxidative damage. Thus, the signaling mechanisms within mitochondria, and between the organelle and its environment, have gained interest as potential drug targets. Here, we discuss redox events in mitochondria that lead to retrograde signaling, the role of redox events in disease, and their potential to serve as therapeutic targets.

Dr. Joe McCord (Ph.D. 1970) is recognized here as a Redox Pioneer because he has published at least three articles on antioxidant/redox biology as first/last author that have been cited over 1000 times and has published at least 37 articles each cited over 100 times. Dr. McCord is known for the monumental discovery of the antioxidant superoxide dismutase (SOD) while a graduate student under fellow redox pioneer Irwin Fridovich and demonstrating its necessity to aerobic life. Beyond this, McCord's career is distinguished for bridging the gap from basic science to clinical relevance by showing the application of SOD and superoxide to human physiology, and characterizing the physiological functions of superoxide in inflammation, immunological chemotaxis, and ischemia-reperfusion injury, among other disease conditions. Work by McCord serves as the foundation upon which our understanding of how superoxide functions in a variety of physiological systems is built and demonstrates how superoxide is essential to aerobic life, yet, if left unchecked by SOD, toxic to a multitude of systems. These discoveries have substantial significance in a wide range of studies with applications in cardiovascular disease, cancer, neurology, and medicine, as well as general health and longevity. Dr. McCord's contributions to free radical biology have been recognized through many prestigious achievement awards, honorary titles, and conferences around the world; each serving as a testament to his status as a redox pioneer.