Deciphering the emerging functions of succinate dehydrogenase in controlling inflammation – SuccINNATE

Succinate dehydrogenase (SDH) is a key mitochondrial enzyme in the tricarboxylic acid (TCA) and the electron transport chain. Germline mutations in SDH subunit genes predispose to paraganglioma and pheochromocytoma (PPGL) by metabolic and epigenetics means. However, our recent published work identified SDH as an important metabolic node of innate immune cell activation and SDH subunits genes mutations were associated to immune disorders. This raise the question of the regulation of inflammation by SDH and its contribution to pathophysiological processes. Using recently developed tools, we will determine the mechanism by which SDH controls inflammatory genes expression and reveal the functional implications of SDH-regulated sterile and non-sterile inflammation models. The project benefits from the synergy of expertise of the laboratories in metabolism and immunology.