Protein succinylation mechanisms and potential targeted therapies in urinary disease.

Abstract

Succinylation is a relatively common post-translational modification. It occurs in the cytoplasm, mitochondria, and the nucleus, where its essential precursor, succinyl-CoA, is present, allowing for the modification of non-histone and histone proteins. In normal cells, succinylation levels are carefully regulated to sustain a dynamic balance, necessitating the involvement of various regulatory mechanisms, including non-enzymatic reactions, succinyltransferases, and desuccinylases. Among these regulatory factors, sirtuin 5, the first identified desuccinylase, plays a significant role and has been extensively researched. The level of succinylation has a significant effect on multiple metabolic pathways, including the tricarboxylic acid cycle, redox balance, and fatty acid metabolism. Dysregulated succinylation can contribute to the progression or exacerbation of various urinary diseases. Succinylation predominantly affects disease progression by altering the expression of key genes and modulating the activity of enzymes involved in vital metabolic processes. Desuccinylases primarily affect enzymes associated with Warburg's effect, thereby affecting the energy supply of tumor cells, while succinyltransferases can regulate gene transcription to alter cell phenotype, thereby involving the development of urinary diseases. Considering these effects, targeting succinylation-related enzymes to regulate metabolic pathways or gene expression may offer a promising therapeutic strategy for treating urinary diseases.