TY - JOUR A2 - Filomeni, Giuseppe AU - Cardaci, Simone AU - Ciriolo, Maria Rosa PY - 2012 DA - 2012/07/19 TI - TCA Cycle Defects and Cancer: When Metabolism Tunes Redox State SP - 161837 VL - 2012 AB - Inborn defects of the tricarboxylic acid (TCA) cycle enzymes have been known for more than twenty years. Until recently, only recessive mutations were described which, although resulted in severe multisystem syndromes, did not predispose to cancer onset. In the last ten years, a causal role in carcinogenesis has been documented for inherited and acquired alterations in three TCA cycle enzymes, succinate dehydrogenase (SDH), fumarate hydratase (FH), and isocitrate dehydrogenase (IDH), pointing towards metabolic alterations as the underlying hallmark of cancer. This paper summarizes the neoplastic alterations of the TCA cycle enzymes focusing on the generation of pseudohypoxic phenotype and the alteration of epigenetic homeostasis as the main tumor-promoting effects of the TCA cycle affecting defects. Moreover, we debate on the ability of these mutations to affect cellular redox state and to promote carcinogenesis by impacting on redox biology. SN - 1687-8876 UR - https://doi.org/10.1155/2012/161837 DO - 10.1155/2012/161837 JF - International Journal of Cell Biology PB - Hindawi Publishing Corporation KW - ER -