Dear Editor,

Succinic acid, once considered merely a tricarboxylic acid cycle intermediate,¹ has been recognized for its significant role in influencing mitochondrial reactive oxygen species homeostasis.² This is largely mediated through the G protein-coupled succinate receptor (SUCR1, also known as GPR91), which has emerged as a vital link connecting metabolic status to a myriad of physiological and pathological processes. SUCR1 is intricately involved in the regulation of blood pressure,³ angiogenesis,⁴ inflammation,⁵ and has been implicated in the pathogenesis of liver fibrosis,⁶ hypertension, and rheumatic arthritis.⁶ These multifaceted roles highlight the receptor’s potential as a promising therapeutic target for a wide spectrum of diseases. However, the molecular mechanisms underlying SUCR1’s activation by various ligands and its subsequent interaction with the inhibitory G protein (G_i) have remained elusive, hindering our comprehensive understanding of its broad physiological significance and therapeutic potential.

 亲爱的编辑，

琥珀酸曾经被认为只是一种三羧酸循环中间体， ¹ 已因其在影响线粒体活性氧稳态中的重要作用而得到认可。 ² 这主要是通过 G 蛋白偶联琥珀酸受体（SUCR1，也称为 GPR91）介导的，该受体已成为连接代谢状态与无数生理和病理过程的重要纽带。 SUCR1 错综复杂地参与血压调节、 ³ 血管生成、 ⁴ 炎症、 ⁵ 并与肝纤维化的发病机制有关， ⁶ 高血压、风湿性关节炎。 ⁶ 这些多方面的作用凸显了该受体作为多种​​疾病的有希望的治疗靶点的潜力。然而，SUCR1 被各种配体激活及其随后与抑制性 G 蛋白 (G) 相互作用的分子机制仍然难以捉摸，阻碍了我们对其广泛的生理意义和治疗潜力的全面理解。