Plenary Lectures

In human and animal cells transcriptional responses to hypoxia are transduced by the HIF (hypoxia inducible factor) hydroxylase pathway.In this system, oxygen sensitive signals are generated by the catalytic action of a set of 2-oxoglutarate dependent dioxygenases that hydroxylate specific prolyl and asparaginyl residues to promote the proteolytic destruction and inactivation of (HIF)-alpha sub-units.In hypoxia this process is suppressed allowing HIF to escape destruction, and bind to hypoxia response elements in DNA.This activates an extensive transcriptional cascade that mediates many cellular and systemic responses to hypoxia, including erythropoiesis, angiogenesis, alterations in matrix metabolism, metabolic reprogramming, and inflammatory/immune signalling.The HIF hydroxylase transcriptional pathway also interacts with other oxygen sensing systems including the electrophysiological excitable oxygen chemo-sensitive cells that control breathing and a newly defined N-Cysteine dioxygenase N-degron system that controls G-protein signals via RGS proteins.The lecture will consider the implications of these findings for physiology and medicine.