SUCNR1

Description

The SUCNR1 (succinate receptor 1) is a protein-coding gene located on chromosome 3.

Succinate receptor 1 (SUCNR1), previously known as G protein-coupled receptor 91 (GPR91), is a receptor activated by succinate, the anionic form of the dicarboxylic acid, succinic acid. Succinate and succinic acid readily convert into each other by gaining (succinate) or losing (succinic acid) protons (H+). Succinate is the predominant form in living organisms. Succinate is an intermediate metabolite in the citric acid cycle (TCA cycle), a metabolic pathway occurring in the mitochondria of virtually all eukaryotic cells. This cycle releases energy stored in nutrient carbohydrates, fats, and proteins. Recent studies indicate that some TCA cycle metabolites regulate various physiological and pathological functions in different cell types. Succinyl CoA in the cycle can release its bound succinate, making succinate a mitochondrial-formed bioactive metabolite. SUCNR1 is a G protein-coupled receptor (GPR). GPRs are cell surface receptors that bind to specific ligands, activating them to elicit responses in their parent cells.

SUCNR1, also known as GPR91 and P2Y purinoceptor 1-like, is a G protein-coupled receptor for succinate. It can mediate signaling through Gq/GNAQ or Gi/GNAI second messengers, depending on the cell type and the processes being regulated. Succinate-SUCNR1 signaling links metabolic stress, inflammation, and energy homeostasis. In macrophages, it plays a variety of immune-regulatory roles, acting as either an anti-inflammatory mediator or a pro-inflammatory booster depending on the inflammatory status of the cell. It hyperpolarizes M2 macrophages versus M1 phenotype through Gq signaling by regulating the transcription of immune function genes. In activated M1 macrophages, it plays a pro-inflammatory role in response to LPS. SUCNR1 is expressed in dendritic cells where it senses immunological danger and enhances immunity. It mediates succinate-triggered intracellular calcium mobilization, induces migratory responses, and acts synergistically with Toll-like receptor ligands to produce proinflammatory cytokines and enhance antigen-specific activation of helper T cells. In the small intestine, SUCNR1 mediates the activation of tuft cells by dietary succinate and triggers type 2 immunity. In adipocytes, SUCNR1 plays a crucial role in energy metabolism control. In response to succinate, it controls leptin expression in an AMPK-JNK-CEBPA-dependent and circadian clock-regulated manner. In muscle tissue, SUCNR1 is expressed in non-muscle cells and coordinates muscle remodeling in response to succinate produced during exercise training in a paracrine manner. In the retina, SUCNR1 mediates vessel growth during retinal development. In response to succinate, it regulates the production of angiogenic factors, including VEGF, by retinal ganglion neurons. {ECO:0000250|UniProtKB:Q6IYF9, ECO:0000250|UniProtKB:Q99MT6, ECO:0000269|PubMed:15141213, ECO:0000269|PubMed:18820681, ECO:0000269|PubMed:23770096, ECO:0000269|PubMed:34133934}

SUCNR1 is also known as GPR91.

Associated Diseases

WES Whole Exome Sequencing