Acylspermidines are conserved mitochondrial sirtuin-dependent metabolites.

ABSTRACT: Sirtuins are nicotinamide adenine dinucleotide (NAD⁺)-dependent protein lysine deacylases regulating metabolism and stress responses; however, characterization of the removed acyl groups and their downstream metabolic fates remains incomplete. Here we employed untargeted comparative metabolomics to reinvestigate mitochondrial sirtuin biochemistry. First, we identified N-glutarylspermidines as metabolites downstream of the mitochondrial sirtuin SIR-2.3 in Caenorhabditis elegans and demonstrated that SIR-2.3 functions as a lysine deglutarylase and that N-glutarylspermidines can be derived from O-glutaryl-ADP-ribose. Subsequent targeted analysis of C. elegans, mouse and human metabolomes revealed a chemically diverse range of N-acylspermidines, and formation of N-succinylspermidine

SUBMITTER: Zhang B 

PROVIDER: S-EPMC11715332 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature