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Lysine propionylation modification (Kpr) plays an important role in the pathogenesis of several cardiovascular diseases, but the role of Kpr in postoperative atrial fibrillation (POAF) is unclear. Here, we established an atlas of proteomics and propionylation proteomics in the atrial appendage tissues from 28 CABG patients, exploring the role of Kpr proteins in the occurrence of POAF. The Kpr of ALDH6A1 was most significantly increased on Lys113 (2.25 folds). The activity of ALDH6A1 increased due to higher binding energy of propionylated ALDH6A1 and NAD, causing an increase in NADH levels in cells and triggering abnormal energy metabolism. Furthermore, the increase in NADH levels triggered the accumulation of reactive oxygen species, which may cause oxidative stress, resulting in the development of AF. This study reveals the important role of ALDH6A1-NADH pathway in POAF, and provides new insights for exploring the pathogenesis of POAF in CABG.
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http://dx.doi.org/10.1038/s42003-025-08264-9 | DOI Listing |
J Biol Chem
August 2025
Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, Paris, France. Electronic address:
In addition to histone acetylation, histone lysine propionylation (such as the H3K18Pr mark) has recently attracted significant attention as a common and abundant modification linking the cellular metabolic state and gene expression. CREB-binding protein (CREBBP) and EP300 are key histone acetyltransferases that play a critical role in gene expression through their catalytic activity. Although CREBBP and EP300 are homologous enzymes with high structural similarities, they exhibit both redundant and specific functions.
View Article and Find Full Text PDFResults Probl Cell Differ
July 2025
Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
Bromodomain and PHD finger-containing protein 1 (BRPF1) is an essential epigenetic regulator and plays a key role in post-translational modification of histones. It is a chromatin reader that recognizes acetylated histones and interacts with the paralogous lysine acetyltransferases KAT6A and KAT6B to promote histone acetylation and related acylations, such as propionylation, at lysine 23 of histone H3, thereby influencing gene expression and regulating developmental programs. BRPF1 contributes to a variety of cellular processes such as cell cycle progression, cell proliferation, cell differentiation, and responses to cellular stresses, including DNA damage.
View Article and Find Full Text PDFBranched-chain amino acid (BCAA) catabolism contributes prominently to the TCA cycle in the healthy pancreas but is suppressed in pancreatic ductal adenocarcinoma (PDA). The impact of this metabolic remodeling on cancer phenotypes remains poorly understood. Here, we find that the BCAA isoleucine is a primary source of propionyl-CoA in PDA cells.
View Article and Find Full Text PDFCommun Biol
June 2025
Department of Cardiovascular Surgery & The Institute of Cardiovascular Diseases, TEDA International Cardiovascular Hospital, Tianjin University & Chinese Academy of Medical Sciences, Tianjin, China.
Lysine propionylation modification (Kpr) plays an important role in the pathogenesis of several cardiovascular diseases, but the role of Kpr in postoperative atrial fibrillation (POAF) is unclear. Here, we established an atlas of proteomics and propionylation proteomics in the atrial appendage tissues from 28 CABG patients, exploring the role of Kpr proteins in the occurrence of POAF. The Kpr of ALDH6A1 was most significantly increased on Lys113 (2.
View Article and Find Full Text PDFProteins
June 2025
Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, USA.
Lysine acylation is a rapidly expanding class of post-translational modifications with largely unexplored functional roles; the study of acylations beyond acetylation is especially impeded by limited methods for their preparation, detection, and characterization in vitro. We previously reported a nuclear magnetic resonance (NMR)-based approach to monitor Nε-lysine acetylation following Ada2/Gcn5-catalyzed installation of a C-acetyl probe on the histone H3 tail. Building on this foundation, here we expand those techniques by demonstrating the installation and H, C-HSQC based NMR detection of both C-acetyl and C-propionyl probes on the histone H4 tail using a mutant p300 lysine acetyltransferase (KAT) enzyme with enhanced activity.
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