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International Journal of Cell Biology
Volume 2012, Article ID 161837, 9 pages
Review Article

TCA Cycle Defects and Cancer: When Metabolism Tunes Redox State

1Department of Biology, University of Rome “Tor Vergata”, Via della Ricerca Scientifica, 00133 Rome, Italy
2IRCCS San Raffaele Pisana, Via di Val Cannuta, 00166 Rome, Italy

Received 13 April 2012; Revised 1 June 2012; Accepted 15 June 2012

Academic Editor: Giuseppe Filomeni

Copyright © 2012 Simone Cardaci and Maria Rosa Ciriolo. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.