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

A fascinating link between sterols and molecular oxygen (O2) 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 O2. Synthesis of sterols by eukaryotes is an O2-intensive process. In this review, we argue that increased levels of O2 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 O2. The idea that nature crafted sterols as a feedback loop to adapt to, or help protect against, the hazards of O2 is novel and enticing. We marshal several lines of evidence to support this thesis: (1) coincidence of atmospheric O2 and sterol evolution; (2) sterols regulate O2 entry into eukaryotic cells and organelles; (3) sterols act as O2 sensors across eukaryotic life; (4) sterols serve as a primitive cellular defence against O2 (including reactive oxygen species). Therefore, sterols may have evolved in eukaryotes partially as an adaptive response to the rise of terrestrial O2, rather than merely as a consequence of it.