The dawn of succinylation: a posttranslational modification

Abstract

Posttranslational modifications affect almost all proteins and are critical to a well-functioning and diverse proteome; however, many modifications remain relatively unknown and unstudied. This paper will give a perspective on the rapidly developing, novel posttranslational modification called succinylation. This modification may be implicated in numerous diseases, such as hepatic, cardiac, and pulmonary diseases. Although the influences of this modification still remain poorly understood, we are confident that further research into succinylation will provide an enhanced understanding of the complex machinery within the mitochondria, as well as the imposing consequences associated with its dysfunction.

Keywords: metabolism; mitochondria; modification; posttranslational; sirtuin 5; succinylation.

Fig. 1.

As explored by Rardin et al., Sirt5 influences HMGCS2, the rate-limiting protein of ketogenesis, through desuccinylation. The study found that the negative charge provided by a succinyl group strongly inhibits the function of HMGCS2 (24). Additionally, lysine residues near the substrate binding site were found to be hypersuccinylated. This is one of the many different proteins and pathways that may be influenced by succinylation.