Mechanisms Involved in Pathological Succinate-Mediated Signaling

Succinate is a key intermediate of the Krebs cycle, which has increasing recognition for its roles beyond energy metabolism, including inflammation, cellular signaling, and metabolic regulation. Extracellular succinate, in particular, has been recognized as a signaling molecule that acts via the succinate receptor 1 (SUCNR1). SUCNR1-mediated signaling, however, demonstrates significant heterogeneity across various pathological contexts, resulting in varied and occasionally contradictory biological outcomes. This complexity underscores the context-dependent characteristics of succinate signaling and its significance in disease progression. This review will offer a comprehensive analysis of the signaling pathways activated during the interaction of succinate with its receptor in various tissues, as well as the potential of succinate regulation to ameliorate several pathological conditions.