Deciphering the Mechanism of Metabolite Toxicity in Inborn Errors of Metabolism (IEM)

Toxic accumulation of metabolites and metabolite intermediates is commonly observed in metabolic disorders. Acute or progressive accumulation of toxic compounds can occur due to a metabolic block but also high plasma levels of particular metabolites (i.e. lipotoxicity, vitamin A toxicity). Even though the etiology of these disorders is well characterized, it is unclear why accumulation of certain metabolites is toxic and whether cells can adapt to the metabolite overload. We aim to uncover the molecular basis for the metabolite toxicity but also identify molecular pathways most important for coping with the toxic metabolite accumulation.