Lysine Malonylation and Its Links to Metabolism and Diseases

Abstract

Malonylation is a recently identified post-translational modification with malonyl-coenzyme A as the donor. It conserved both in prokaryotes and eukaryotes. Recent advances in the identification and quantification of lysine malonylation by bioinformatic analysis have improved our understanding of its role in the regulation of protein activity, interaction, and localization and have elucidated its involvement in many biological processes. Malonylation has been linked to diverse physiological processes, including metabolic disorders, inflammation, and immune regulation. This review discusses malonylation in theory, describes the underlying mechanism, and summarizes the recent progress in malonylation research. The latest findings point to novel functions of malonylation and highlight the mechanisms by which malonylation regulates a variety of cellular processes. Our review also marks the association between lysine malonylation, the enzymes involved, and various diseases, and discusses promising diagnostic and therapeutic biomolecular targets for future clinical applications.

Localization and Quantification of Post-Translational Modifications of Proteins Using Electron Activated Dissociation Fragmentation on a Fast-Acquisition Time-of-Flight Mass Spectrometer

“…Strikingly, we showed for electron-based fragmentation preserves the integrity of the malonyl groups on peptides. Malonylation has been reported to be associated with a plethora of diseases, including metabolic diseases, neurodegenerative diseases, diabetes, cardiovascular disease, cancers, and osteoarthritis . Novel proteomics workflows to confidently and accurately profile lysine malonyl in samples are thus highly biologically relevant.…”

“…Malonylation has been reported to be associated with a plethora of diseases, including metabolic diseases, neurodegenerative diseases, diabetes, cardiovascular disease, cancers, and osteoarthritis. 35 Novel proteomics workflows to confidently and accurately profile lysine malonyl in samples are thus highly biologically relevant. Indeed, obtaining confident and precise information on PTM identification, site localization, and quantification is essential to understand how proteins are affected by modifications and to gain deeper insights into biological processes and disease mechanisms.…”

Functions and mechanisms of protein lysine butyrylation (Kbu): Therapeutic implications in human diseases

“…Although some reports indicate that Kbu modification is associated with some diseases, the specific relationship between the regulation of Kbu modification and the occurrence and development of diseases remains unclear, and the relationship between Kbu modification and disease regulation needs further exploration. 94 , 95 …”

Orthogonal Translation for Site-Specific Installation of Post-translational Modifications

“…Lysine succinylation, malonylation, and glutarylation are three PTMs found in both histones and nonhistone proteins from eukaryotic and bacterial cells. − They are mostly involved in cellular metabolism and stress responses . A special feature of these three lysine PTMs is that they change lysine residues from positively charged to negatively charged, making them distinct from other lysine acylation.…”