Coenzyme A, protein CoAlation and redox regulation in mammalian cells.

Ivan Gout

doi:10.1042/bst20170506

Abstract

In a diverse family of cellular cofactors, coenzyme A (CoA) has a unique design to function in various biochemical processes. The presence of a highly reactive thiol group and a nucleotide moiety offers a diversity of chemical reactions and regulatory interactions. CoA employs them to activate carbonyl-containing molecules and to produce various thioester derivatives (e.g. acetyl CoA, malonyl CoA and 3-hydroxy-3-methylglutaryl CoA), which have well-established roles in cellular metabolism, production of neurotransmitters and the regulation of gene expression. A novel unconventional function of CoA in redox regulation, involving covalent attachment of this coenzyme to cellular proteins in response to oxidative and metabolic stress, has been recently discovered and termed protein CoAlation (S-thiolation by CoA or CoAthiolation). A diverse range of proteins was found to be CoAlated in mammalian cells and tissues under various experimental conditions. Protein CoAlation alters the molecular mass, charge and activity of modified proteins, and prevents them from irreversible sulfhydryl overoxidation. This review highlights the role of a key metabolic integrator CoA in redox regulation in mammalian cells and provides a perspective of the current status and future directions of the emerging field of protein CoAlation.

Highlights

In a diverse family of cellular cofactors, coenzyme A (CoA) has a unique design to function in various biochemical processes
A classical pathway for CoA biosynthesis involves five enzymatic steps that are highly conserved from prokaryotes to eukaryotes and utilise pantothenate, adenosine triphosphate (ATP) and cysteine (Figure 1A) [1]
It has been proposed that intracellular CoA pools could be replenished through the degradation of external sources of CoA by ectonucleotide pyrophosphatases (ENPPs) to 40-phosphopantetheine (P-PanSH), which is transported into a cell and incorporated in the CoA biosynthetic pathway downstream of phosphopantothenoylcysteine decarboxylase (PPCDC) [3]

Summary

Introduction

In a diverse family of cellular cofactors, coenzyme A (CoA) has a unique design to function in various biochemical processes. The biosynthesis and homeostasis of CoA is controlled at different levels: transcription of genes encoding biosynthetic enzymes, regulation of enzymatic activities by a feedback mechanism, signalling pathways, degradation of CoA and interconversion between CoA and its thioester derivatives. CoA and its thioester derivatives play important roles in numerous biosynthetic and degradative pathways of cellular metabolism, allosteric interactions and the regulation of gene expression.

Results

Conclusion