Oxygen toxicity and the health and survival of eukaryote cells: a new piece is added to the puzzle.

Abstract

My first thought was “Superoxide dismutase: of what use is that to a cell?” It was 1976 and I was a graduate student in search of a topic for a “literature” seminar. Fortunately I chose to present the story of this exotic-sounding protein, “SOD,” to my colleagues and was rewarded with the beginnings of a long-term fascination with the concept that our aerobic (O2-based) lifestyle is fraught with oxidative (O2-based) hazards. This concept is now firmly linked to topics of enduring interest and importance such as aging, cancer, ischemia (anoxic tissue damage), aerotolerance, and immune system function. In this issue of PNAS, Luk et al . (1), using brewer's yeast cells, show how a key eukaryote antioxidant enzyme, mitochondrial Mn-cofactored SOD (SOD2), acquires its Mn cofactor and possibly its active conformation via a previously uncharacterized nuclear-encoded protein, thus providing both a tool for experimental oxy-radical stress manipulations and a more detailed understanding of how eukaryote cell oxygen defenses are assembled. By the 1960s it was clear that reactive oxygen species (ROS), namely, partially reduced O2 derivatives such as hydrogen peroxide (H2O2), the hydroxyl radical (*OH), and the superoxide anion radical (O2-) formed by ionizing radiation could oxidize and damage cell proteins, lipids, and nucleic acids. However, there was little convincing evidence that either O2-mediated damage or ROS were produced by normal respiratory (dioxygen-reducing) cellular processes. This changed in 1969 when McCord and Fridovich (2) demonstrated that the catalytic activity of a long-known red blood cell protein of unknown function, erythrocuprein, was to specifically dismute O2- to H2O2 and O2. If O2- were not a real and present danger, why would red cells contain an enzyme specifically degrading it? …