Succinate, once considered a mere intermediate in the tricarboxylic acid (TCA) cycle, has emerged as a critical mediator in inflammation. Disruptions in the TCA cycle lead to succinate accumulation in the mitochondrial matrix, which then diffuses into the cytosol and extracellular space. Elevated cytosolic succinate stabilizes hypoxia-inducible factor-1α (HIF-1α) by inhibiting prolyl hydroxylases, enhancing inflammatory responses. Succinate also acts extracellularly as a signaling molecule by engaging succinate receptor 1 (SUCNR1) on immune cells, modulating their pro-inflammatory or anti-inflammatory activities. Alterations in succinate levels are associated with various inflammatory disorders, including rheumatoid arthritis, inflammatory bowel disease, obesity, and atherosclerosis. Targeting succinate pathways offers promising therapeutic avenues for these diseases. Succinate is produced from α-ketoglutarate through a two-step process involving α-ketoglutarate dehydrogenase and succinyl-CoA synthetase. Under conditions like immune cell activation or tumorigenesis, alternative pathways lead to succinate accumulation. Succinate is transported from the mitochondrial matrix to the cytosol and extracellular space via specialized transporters. Intracellular succinate stabilizes HIF-1α, promoting pro-inflammatory gene expression. Extracellular succinate activates SUCNR1, which can have both pro- and anti-inflammatory effects depending on the context. Succinate plays a pivotal role in inflammation by linking metabolism and immune regulation. It influences various immune cells, including macrophages, dendritic cells, and T cells, through different mechanisms. In macrophages, succinate enhances pro-inflammatory responses, while in anti-inflammatory macrophages, it can promote anti-inflammatory activities. In dendritic cells, succinate promotes maturation and antigen presentation, enhancing immune responses. In T cells, succinate can inhibit degranulation and cytokine secretion, affecting immune responses. Dysregulated succinate metabolism is linked to various diseases, including rheumatoid arthritis, inflammatory bowel disease, obesity, and atherosclerosis. Targeting succinate metabolism through enzyme inhibitors like malonate and itaconate, or by modulating SUCNR1 activity, offers potential therapeutic strategies. These approaches aim to regulate succinate levels and mitigate the detrimental effects of excessive succinate accumulation. The study highlights the complex roles of succinate in inflammation and its potential as a therapeutic target. Understanding the mechanisms of succinate metabolism and its signaling pathways is crucial for developing effective interventions in inflammatory diseases. Further research is needed to fully elucidate the intracellular and extracellular functions of succinate and to explore its therapeutic potential.Succinate, once considered a mere intermediate in the tricarboxylic acid (TCA) cycle, has emerged as a critical mediator in inflammation. Disruptions in the TCA cycle lead to succinate accumulation in the mitochondrial matrix, which then diffuses into the cytosol and extracellular space. Elevated cytosolic succinate stabilizes hypoxia-inducible factor-1α (HIF-1α) by inhibiting prolyl hydroxylases, enhancing inflammatory responses. Succinate also acts extracellularly as a signaling molecule by engaging succinate receptor 1 (SUCNR1) on immune cells, modulating their pro-inflammatory or anti-inflammatory activities. Alterations in succinate levels are associated with various inflammatory disorders, including rheumatoid arthritis, inflammatory bowel disease, obesity, and atherosclerosis. Targeting succinate pathways offers promising therapeutic avenues for these diseases. Succinate is produced from α-ketoglutarate through a two-step process involving α-ketoglutarate dehydrogenase and succinyl-CoA synthetase. Under conditions like immune cell activation or tumorigenesis, alternative pathways lead to succinate accumulation. Succinate is transported from the mitochondrial matrix to the cytosol and extracellular space via specialized transporters. Intracellular succinate stabilizes HIF-1α, promoting pro-inflammatory gene expression. Extracellular succinate activates SUCNR1, which can have both pro- and anti-inflammatory effects depending on the context. Succinate plays a pivotal role in inflammation by linking metabolism and immune regulation. It influences various immune cells, including macrophages, dendritic cells, and T cells, through different mechanisms. In macrophages, succinate enhances pro-inflammatory responses, while in anti-inflammatory macrophages, it can promote anti-inflammatory activities. In dendritic cells, succinate promotes maturation and antigen presentation, enhancing immune responses. In T cells, succinate can inhibit degranulation and cytokine secretion, affecting immune responses. Dysregulated succinate metabolism is linked to various diseases, including rheumatoid arthritis, inflammatory bowel disease, obesity, and atherosclerosis. Targeting succinate metabolism through enzyme inhibitors like malonate and itaconate, or by modulating SUCNR1 activity, offers potential therapeutic strategies. These approaches aim to regulate succinate levels and mitigate the detrimental effects of excessive succinate accumulation. The study highlights the complex roles of succinate in inflammation and its potential as a therapeutic target. Understanding the mechanisms of succinate metabolism and its signaling pathways is crucial for developing effective interventions in inflammatory diseases. Further research is needed to fully elucidate the intracellular and extracellular functions of succinate and to explore its therapeutic potential.