Special relationship between sterols and oxygen: Were sterols an adaptation to aerobic life?

A fascinating link between sterols and molecular oxygen (O-2) has been a common thread running through the fundamental work of Konrad Bloch, who elucidated the biosynthetic pathway for cholesterol, to recent work supporting a role of sterols in the sensing of O-2. Synthesis of sterols by eukaryotes is an O-2-intensive process. In this review, we argue that increased levels of O-2 in the atmosphere not only made the evolution of sterols possible, but that these sterols may in turn have provided the eukaryote with an early defence mechanism against O-2. The idea that nature crafted sterols as a feedback loop to adapt to, or help protect against, the hazards of O-2 is novel and enticing. We marshal several lines of evidence to support this thesis: (1) coincidence of atmospheric O-2 and sterol evolution; (2) sterols regulate O-2 entry into eukaryotic cells and organelles; (3) sterols act as O-2 sensors across eukaryotic life; (4) sterols serve as a primitive cellular defence against O-2 (including reactive oxygen species). Therefore, sterols may have evolved in eukaryotes partially as an adaptive response to the rise of terrestrial O-2, rather than merely as a consequence of it. (C) 2009 Elsevier Inc. All rights reserved.