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It is found that succinic acid, once considered merely a tricarboxylic acid cycle intermediate, has been recognized for its significant role in influencing mitochondrial reactive oxygen species homeostasis. This is largely mediated through the G protein-coupled succinate receptor (SUCR1, also known as GPR91). A 2004 paper published in Nature identified succinate as the endogenous ligand of SUCR1.
More than a decade of research found that activation of SUCR1 had been implicated in the pathogenesis of liver fibrosis, hypertension, and rheumatic arthritis. Therefore, it is important to study the molecular mechanisms underlying SUCR1’s recognition and activation by ligands for understanding its physiological significance and therapeutic potentials as a target. In June 2024, Huaqiang Xu from Shanghai Institute of Materia Medica Chinese Academy of Sciences and Wei Fu from Fudan University published a paper on Cell Research, titled Molecular basis of ligand recognition and activation of the human succinate receptor SUCR1, reporting the unique ligand binding features and activation mechanism of human SUCR1.
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