Redox Signaling by Reactive Electrophiles and Oxidants

Saba Parvez#, Marcus J. C. Long#, Jesse Poganik, and Yimon Aye*

(#, co-first authors. *, corresponding author)

Chemical Reviews (American Chemical Society) — just accepted

The concept of cell signaling in the context of non-enzyme-assisted protein modifications by reactive electrophilic and oxidative species—broadly known as redox signaling—is a uniquely complex topic that has been approached from numerous different and multidisciplinary angles. Our Review reflects on 5 aspects critical for understanding how Nature harnesses these non-canonical post-translational modifications to coordinate distinct cellular activities: (1) specific players and their generation; (2) physicochemical properties; (3) mechanisms of action; (4) methods of interrogation; and (5) functional roles in health and disease. Emphasis is primarily placed on the latest progress in the field, but several aspects of classical work likely forgotten/lost are also recollected. For researchers with interests in getting into the field, our Review is anticipated to function as a primer. For the expert, we aim to stimulate thought and discussion about fundamentals of redox signaling mechanisms, and nuances of specificity/selectivity and timing in this sophisticated yet fascinating arena at the crossroads of chemistry and biology.