Abstract
Dictyostelium discoideum (D. discoideum) is a simple eukaryote with a unique life cycle in which it differentiates from unicellular amoebae into a fruiting body upon starvation. Reactive oxygen species (ROS) have been associated with bacterial predation, as well as regulatory events during D. discoideum development and differentiation. Coenzyme A (CoA) is a key metabolic integrator in all living cells. A novel function of CoA in redox regulation, mediated by covalent attachment of CoA to cellular proteins in response to oxidative or metabolic stress, has been recently discovered and termed protein CoAlation. In this study, we report that the level of CoA and protein CoAlation in D. discoideum are developmentally regulated, and correlate with the temporal expression pattern of genes implicated in CoA biosynthesis during morphogenesis. Furthermore, treatment of growing D. discoideum cells with oxidising agents results in a dose-dependent increase of protein CoAlation. However, much higher concentrations were required when compared to mammalian cells and bacteria. Increased resistance of D. discoideum to oxidative stress induced by H2O2 has previously been attributed to high levels of catalase activity. In support of this notion, we found that H2O2-induced protein CoAlation is significantly increased in CatA-deficient D. discoideum cells. Collectively, this study provides insights into the role of CoA and protein CoAlation in the maintenance of redox homeostasis in amoeba and during D. discoideum morphogenesis.
Highlights
Coenzyme A (CoA) is a fundamental and ubiquitous cellular cofactor, and functions as a carbonyl-activating group and an acyl group carrier in diverse biological processes
We found that H2O2-induced protein CoAlation is significantly increased in CatA-deficient D. discoideum cells
These findings indicate that changes in the level of CoA and protein CoAlation are associated with redox regulation when D. discoideum cells are exposed to oxidative and metabolic stress
Summary
Coenzyme A (CoA) is a fundamental and ubiquitous cellular cofactor, and functions as a carbonyl-activating group and an acyl group carrier in diverse biological processes. CoA and its thioester derivatives (acetyl-CoA, malonyl-CoA, succinyl-CoA, HMG-CoA etc.) are involved in a wide range of biochemical reactions, including fatty acid metabolism, protein acylation, biosynthesis of amino acids and cholesterol, and the regulation of gene expression [1,2]. The CoA biosynthetic pathway is conserved across eukaryotes and prokaryotes and involves enzymatic conjugation of pantothenate (vitamin B5), cysteine and adenosine triphosphate (ATP) in five consecutive steps. It is modulated in different ways, including the expression of genes encoding for biosynthetic enzymes, regulation of their enzymatic activities, interconversion among CoA and its thioester derivatives and CoA degradation. Dysregulation of CoA biosynthesis and homeostasis has been linked to human pathologies such as cancer, diabetes, neurodegeneration and cardiac hypertrophy [1,3]
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