malonylome

Malonylome refers to the complete set of protein lysine malonylation events in a given cell, tissue, organism, or subcellular compartment under a defined condition. It is part of the broader family of post-translational modifications and is studied with proteomics to understand how malonylation influences metabolism and cellular function. Global mapping of malonylated proteins, or the malonylome, has revealed widespread modification of metabolic enzymes, particularly in mitochondria, suggesting a role in energy production and regulation of fatty acid oxidation.

Malonylation adds a negatively charged malonyl group to lysine residues, which can occur nonenzymatically from malonyl-CoA or, less commonly, via enzymatic transfer. The modification is reversible and is removed by demalonylases such as SIRT5, with other sirtuins possibly contributing in different compartments. Levels of malonylation correlate with cellular metabolic state, reflecting fluctuations in malonyl-CoA availability and nutrient conditions.

Functionally, malonylation can alter enzyme activity, protein stability, and interactions, thereby modulating pathways such as the tricarboxylic acid cycle, oxidative phosphorylation, and fatty acid metabolism. Crosstalk with other PTMs and dynamic regulation by cellular energy status suggest a role in metabolic adaptation and stress responses. Abnormal malonylation patterns have been reported in various disease models, but causal relationships remain under study.

Proteomic approaches to define the malonylome typically combine affinity enrichment for malonyllysine with high-resolution mass spectrometry, enabling site-specific identification and quantification. Data sets are used to infer regulatory networks and to prioritize sites for functional studies. As methods improve, the malonylome concept supports a broader view of how metabolic state links to protein regulation.