Reactive Acyl-CoA Species Modify Proteins and Induce Carbon Stress

• Published in: Trends in biochemical sciences (Amsterdam. Regular ed.) Vol. 43; no. 5; pp. 369 - 379
• Main Authors: Trub, Alec G., Hirschey, Matthew D.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2018
• Subjects: Acyl Coenzyme A - chemistry; Acyl Coenzyme A - metabolism; Animals; Carbon - chemistry; Carbon - metabolism; carbon stress; Humans; metabolism; Oxidative Stress; post-translational modifications; Protein Processing, Post-Translational; reactive acyl-CoA species; reactive oxygen species; Substrate Specificity; metabolism; post-translational modifications; reactive acyl-CoA species; carbon stress; oxidative stress; reactive oxygen species
• ISSN: 0968-0004; 1362-4326
• DOI: 10.1016/j.tibs.2018.02.002

In recent years, our understanding of the scope and diversity of protein post-translational modifications (PTMs) has rapidly expanded. In particular, mitochondrial proteins are decorated with an array of acyl groups that can occur non-enzymatically. Interestingly, these modifying chemical moieties are often associated with intermediary metabolites from core metabolic pathways. In this Review, we describe biochemical reactions and biological mechanisms that activate carbon metabolites for protein PTM. We explore the emerging links between the intrinsic reactivity of metabolites, non-enzymatic protein acylation, and possible signaling roles for this system. Finally, we propose a model of ‘carbon stress’, similar to oxidative stress, as an effective way to conceptualize the relationship between widespread protein acylation, nutrient sensing, and metabolic homeostasis. Several key intermediary metabolites have high intrinsic reactivity. A wide range of reactive acyl-CoA species are able to modify proteins non-enzymatically. High flux through some metabolic pathways lead to cellular increases in reactive acyl-CoA species and result in protein modifications that can impair protein function. Similar to reactive oxygen species, reactive acyl-CoA species may have a signaling role in some contexts, but may be damaging when uncontrolled.