Succinylation participates in the progress of Idiopathic pulmonary fibrosis through mitochondrial energy metabolism

Abstract

Abstract Background A new pathogenic role for mitochondrial dysfunction has been associated with aging and correlated with the development of idiopathic pulmonary fibrosis (IPF). The latest study found that the lysine succinylation (Ksucc) is involved in many energy metabolism pathways and affects the metabolic process in mitochondria, making this modification highly valuable for studying IPF related to mitochondrial dysfunction. We speculate Ksucc participate in IPF progression through mitochondrial energy metabolism pathway. Methods We used liquid chromatography with tandem mass spectrometry (LC-MS/MS) to perform the first global profiling of Ksucc in lung tissues with IPF patients. The changes of candidate key proteins and Ksucc sites related to energy metabolism in IPF lung tissues were analyzed by using the clusters of orthologous groups of proteins (COG), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene ontology (GO). We then compared these proteins with those reported in the literature in normal lung tissues by parallel reaction monitoring (PRM). Results We identified 1964 Ksucc sites in 628 proteins. 675 Ksucc sites in 124 proteins closely related to mitochondrial metabolism. We compared these proteins with those reported in the literature in normal lung tissues to identify differences in 119 proteins and Ksucc sites in mitochondria. 43 Ksucc sites in 27 proteins were associated with energy metabolism. There were differences in the expression of 4 Ksucc sites in 4 proteins between normal and IPF lung tissues. Conclusion Our work expands the Ksucc database in IPF lung and suggested that mitochondrial energy metabolism is involved in the progression of IPF. Ksucc sites of proteins associated with mitochondrial energy metabolism can also serve as candidate molecules for future mechanism exploration and drug target selection in IPF.