Current Opinion in Physiology · May 24, 2022

Mitochondrial lysine acylation and cardiometabolic stress: Truth or consequence?

By Muoio DM, Williams AS, Grimsrud PA

Disruptions in oxidative metabolism are often accompanied by tissue accumulation of catabolic carbon intermediates, including acyl CoA molecules that can react with the epsilon amino group of lysine residues on cellular proteins. In general, acyl-lysine post-translational modifications (PTMs) on mitochondrial proteins correlate negatively with energy homeostasis and are offset by the mitochondrial sirtuins, a prominent family of NAD⁺-dependent deacylases linked favorably to longevity and metabolic resilience. Whereas studies over the past decade elicited widespread conjecture as to the far-reaching regulatory roles of these PTMs, more recent work has stirred controversy in this field of study. This review draws attention to discrepancies in the science, challenges current dogma, and encourages new perspectives on the physiological relevance of mitochondrial lysine acylation.

doi.org/10.1016/j.cophys.2022.100551Open access, accepted manuscriptPubMed 39606008Mechanisms