Higher mitochondrial protein-Succinylation detected in lung tissues of idiopathic pulmonary fibrosis patients

Abstract

A new pathogenic role for mitochondrial dysfunction has been associated with the development of idiopathic pulmonary fibrosis (IPF). Lysine succinylation (Ksucc) is involved in many energy metabolism pathways in mitochondria, making Ksucc highly valuable for studying IPF. We used liquid chromatography with tandem mass spectrometry (LC-MS/MS) to perform the first global profiling of Ksucc in fibrotic lung tissues from IPF patients, providing a proof of concept for the alteration of Ksucc in IPF and highlighting its potential as a therapeutic target. Selected candidate proteins were further verified by targeted proteomics using parallel reaction monitoring (PRM). In this study, we identified 1964 Ksucc sites on 628 modified proteins, with675 of these Ksucc sites on 124 modified proteins closely related to mitochondrial metabolism. 117 succinylated proteins were associated with energy metabolism in mitochondria by comparing these proteins with those previously reported in normal lung tissues. The Ksucc levels in KYAT3, HSD17B8, GRHPR, and IDH2 were different between control and IPF groups by Using PRM. This study provides insight into Ksucc profile alterations in IPF pathogenesis and Ksucc sites in proteins associated with mitochondrial energy metabolism can also serve as candidate molecules for future mechanism exploration and drug target selection in IPF.