Lysine succinylation as a metabolic switch in cardiovascular diseases: Mechanistic insights and therapeutic perspectives

作者：Fei Mu, Haiyue Zhang, Rui Gong, Rui Lin, Meina Zhao, Xingru Tao, Lei Shang, Miaomiao Xi, Jinyi Zhao, Jingwen Wang · 发表于：Redox Biology · 年份：2025 · DOI：10.1016/j.redox.2025.103932 · 被引用次数：3 · 研究领域：Sirtuins and Resveratrol in Medicine、Histone Deacetylase Inhibitors Research、Bioactive natural compounds

Cardiovascular diseases (CVDs) are life-threatening disorders arising from interactions between genetic and environmental factors, imposing a heavy global health burden with high morbidity and mortality. Emerging evidence suggests that dysregulated epigenetic modifications, particularly lysine succinylation, play a critical role in the pathogenesis of CVD. Characterized by the covalent addition of a succinyl group to lysine residues, succinylation dynamically alters the functions of proteins, including those involved in transcriptional regulation, and directly affects energy metabolism, oxidative stress, inflammation, apoptosis, and fibrosis. This modification has been linked to the development of various CVDs, such as atrial fibrillation, myocardial ischemia-reperfusion injury, myocardial infarction, heart failure, aortic aneurysm and dissection, diabetic cardiomyopathy, hypertrophic cardiomyopathy, and atherosclerosis. Its effects on key biological processes contribute to these conditions through multiple mechanisms. This review systematically summarizes current research on the role of succinylation in cardiovascular pathophysiology, with a particular focus on its function as a “metabolic switch” in CVDs. It further highlights the critical role of succinylation in regulating redox homeostasis and maintaining the balance of SIRT5-mediated desuccinylation. By integrating mechanistic insights from preclinical and clinical studies, we aim to provide a comprehensive framework fo...