GEE SEMINAR: Prof Ivan Gout

Seminar Speaker:  Prof Ivan Gout, Department of Structural and Molecular Biology, UCL

‘Coenzyme A biology, but not as we know it’.

Location: G46 HO Schlid Pharm LT, Medical Sciences & Anatomy Building
Host: Chris Thompson

This seminar is open to all regardless of career stage. Please share details with colleagues, wider networks and those who may be interested.

Abstract 

Coenzyme A (CoA) is an essential cofactor in all living cells. CoA and its thioesters participate in diverse anabolic and catabolic pathways, allosteric interactions, biosynthesis of neurotransmitters and the regulation of gene expression. Deregulation of CoA biosynthesis in animal models and inborn mutations in human genes involved in the CoA biosynthetic pathway have been associated with human pathologies, including cancer, neurodegeneration and metabolic disorders.

We have recently discovered the antioxidant function of CoA, involving covalent protein modification by this cofactor and termed it CoAlation. To discover and study protein CoAlation and the antioxidant function of CoA, we have developed several novel reagents and methodologies, including: (a) anti-CoA mAb, which specifically recognize CoA in ELISA, WB, IP and IHC; (b) a robust mass spectrometry-based methodology for the identification of CoAlated proteins; and (c) efficient in vitro CoAlation and deCoAlation assays. They have been employed to demonstrate that protein CoAlation is a reversible and widespread post-translational modification induced by oxidizing agents and metabolic stress in cells, tissues and model organisms. To date, we have identified more than 2300 CoAlated proteins and showed that CoAlation modulates the activity and subcellular localization of modified proteins. It can also protect oxidized cysteine residues from overoxidation and induce significant conformational changes. Based on these findings, we propose that under physiological conditions CoA functions as a key metabolic cofactor but acts as an antioxidant in cellular response to oxidative or metabolic stress. The pattern of protein Coalition has been examined in human pathologies associated with oxidative stress, including neurodegeneration and cancer. Recent advances on defying molecular mechanisms of the CoAlation/deCoAlation cycle and investigating the antioxidant function of CoA in neurodegenerative pathologies (Alzheimer’s and Parkinson’s diseases) will be presented. I will also discuss the evolution of CoA biosynthesis and the role of protein CoAlation and the antioxidant function of CoA in metabolic dormancy and hibernation.