SUCNR1

Succinate receptor 1 (SUCNR1), also known as GPR91, is a G protein‑coupled receptor that binds extracellular succinate, a metabolite of the tricarboxylic acid (TCA) cycle. It acts as a sensor of metabolic stress, linking changes in cellular energy status to physiological signaling. SUCNR1 is expressed in multiple tissues, including the kidney (notably juxtaglomerular cells), adipose tissue, liver, retina, and various immune and vascular cells.

Signal transduction through SUCNR1 is primarily via Gq/11 proteins, leading to phospholipase C activation and intracellular calcium mobilization, with downstream effects such as ERK1/2 signaling. In some cell types, coupling to other G proteins (e.g., Gi/o) or β-arrestin pathways has been reported, reflecting context-dependent signaling.

Functions attributed to SUCNR1 include regulation of renal renin release, contributing to the control of blood pressure and renal perfusion. In the immune system, SUCNR1 can promote activation and chemotaxis of dendritic cells and macrophages, thereby linking metabolic cues to immune responses. In the retina and other tissues, SUCNR1 signaling can influence angiogenesis and inflammatory processes, particularly under ischemic or hypoxic conditions.

Clinical relevance for SUCNR1 is active in areas such as hypertension, metabolic inflammation, and ischemia‑related diseases. Because extracellular succinate can accumulate during metabolic stress, SUCNR1 is explored as a potential therapeutic target to modulate inflammatory and vascular responses associated with metabolic dysfunction. Research typically employs gene knockout models and pharmacological tools to dissect tissue-specific roles of SUCNR1.