SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways.

Protein function is regulated by diverse posttranslational modifications. The mitochondrial sirtuin SIRT5 removes malonyl and succinyl moieties from target lysines. The spectrum of protein substrates subject to these modifications is unknown.

Mitochondrial SIRT4-type proteins in Caenorhabditis elegans and mammals interact with pyruvate carboxylase and other acetylated biotin-dependent carboxylases.

The biological and enzymatic function of SIRT4 is largely uncharacterized. We show that the Caenorhabditis elegans SIR-2.2 and SIR-2.

C. elegans SIRT6/7 homolog SIR-2.4 promotes DAF-16 relocalization and function during stress.

FoxO transcription factors and sirtuin family deacetylases regulate diverse biological processes, including stress responses and longevity. Here we show that the Caenorhabditis elegans sirtuin SIR-2.4--homolog of mammalian SIRT6 and SIRT7 proteins--promotes DAF-16-dependent transcription and stress-induced DAF-16 nuclear localization.

The first identification of lysine malonylation substrates and its regulatory enzyme.

Protein post-translational modifications (PTMs) at the lysine residue, such as lysine methylation, acetylation, and ubiquitination, are diverse, abundant, and dynamic. They play a key role in the regulation of diverse cellular physiology. Here we report discovery of a new type of lysine PTM, lysine malonylation (Kmal).

Mitochondrial sirtuins in the regulation of mitochondrial activity and metabolic adaptation.

In eukaryotes, mitochondria carry out numerous functions that are central to cellular and organismal health. How mitochondrial activities are regulated in response to differing environmental conditions, such as variations in diet, remains an important unsolved question in biology. Here, we review emerging evidence suggesting that reversible acetylation of mitochondrial proteins on lysine residues represents a key mechanism by which mitochondrial functions are adjusted to meet environmental demands.