Succinate receptor GPR91 is one of G protein‐coupled receptors (GPCRs), and is expressed in a variety of cell types and tissues. Succinate is its natural ligand, and its activation represents that an intrinsic metabolic intermediate exerts a regulatory role on many critical life processes involving pathophysiologic mechanisms, such as innate immunity, inflammation, tissue repair, and oncogenesis. With the illustration of 3‐dimensional crystal structure of the receptor and discovery of its antagonists, it is possible to dissect the succinate‐GPR91‐G protein signaling pathways in different cell types under pathophysiological conditions. Deep understanding of the GPR91‐ligand binding mode with various agonists and antagonists would aid in elucidating the molecular basis of a spectrum of chronic illnesses, such as hypertension, diabetes, and their renal and retina complications, metabolic‐associated fatty liver diseases, such as nonalcoholic steatohepatitis and its fibrotic progression, inflammatory bowel diseases (Crohn's disease and ulcerative colitis), age‐related macular degeneration, rheumatoid arthritis, and progressive behaviors of malignancies. With better delineation of critical regulatory role of the succinate‐GPR91 axis in these illnesses, therapeutic intervention may be developed by specifically targeting this signaling pathway with small molecular antagonists or other strategies.

中文翻译：

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GPR91，一种调节慢性疾病病理生理过程的关键信号机制

琥珀酸受体 GPR91 是 G 蛋白偶联受体 (GPCR) 中的一种，在多种细胞类型和组织中表达。琥珀酸是其天然配体，其活化代表内在代谢中间体对涉及病理生理机制的许多关键生命过程发挥调节作用，例如先天免疫、炎症、组织修复和肿瘤发生。随着受体的 3 维晶体结构的说明及其拮抗剂的发现，有可能在病理生理条件下剖析不同细胞类型中的琥珀酸 GPR91-G 蛋白信号通路。深入了解 GPR91 配体与各种激动剂和拮抗剂的结合模式将有助于阐明一系列慢性疾病的分子基础，如高血压、糖尿病、及其肾脏和视网膜并发症、代谢相关脂肪肝疾病，如非酒精性脂肪性肝炎及其纤维化进展、炎症性肠病（克罗恩病和溃疡性结肠炎）、年龄相关性黄斑变性、类风湿性关节炎和恶性肿瘤的进行性行为。随着对琥珀酸-GPR91 轴在这些疾病中的关键调节作用的更好描述，可以通过使用小分子拮抗剂或其他策略专门针对该信号通路来开发治疗干预。和恶性肿瘤的进行性行为。随着对琥珀酸-GPR91 轴在这些疾病中的关键调节作用的更好描述，可以通过使用小分子拮抗剂或其他策略专门针对该信号通路来开发治疗干预。和恶性肿瘤的进行性行为。随着对琥珀酸-GPR91 轴在这些疾病中的关键调节作用的更好描述，可以通过使用小分子拮抗剂或其他策略专门针对该信号通路来开发治疗干预。