The glyco-redox interplay: Principles and consequences on the role of reactive oxygen species during protein glycosylation

摘要

Reactive oxygen species (ROS) carry out prime physiological roles as intracellular signaling agents, yet pathologically high concentrations of ROS cause irreversible damage to biomolecules, alter cellular programs and contribute to various diseases. While decades of intensive research have identified redox-related patterns and signaling pathways, very few addressed how the glycosylation machinery senses and responds to oxidative stress. A common trait among ROS and glycans residing on glycoconjugates is that they are both highly dynamic, as they are quickly fine-tuned in response to stressors such as inflammation, cancer and infectious diseases. On this account, the delicate balance of the redox potential, which is tightly regulated by dozens of enzymes including NOXs, and the mitochondrial electron transport chain as well as the fluidity of glycan biosynthesis resulting from the cooperation of glycosyltransferases, glycosidases, and nucleotide sugar transporters, is paramount to cell survival. Here, we review the broad spectrum of the interplay between redox changes and glycosylation with respect to their principle consequences on human physiology.