Revisiting the TCA cycle: Signaling to tumor formation

Nuno Raimundo, Bora E. Baysal, Gerald S. Shadel

Research output: Contribution to journalReview articlepeer-review

198 Scopus citations


A role for mitochondria in tumor formation is suggested by mutations in enzymes of the TCA cycle: isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH) and fumarate hydratase (FH). Although they are all components of the TCA cycle, the resulting clinical presentations do not overlap. Activation of the hypoxia pathway can explain SDH phenotypes, but recent data suggest that FH and IDH mutations lead to tumor formation by repressing cellular differentiation. In this review, we discuss recent findings in the context of both mitochondrial and cytoplasmic components of the TCA cycle, and we propose that extrametabolic roles of TCA cycle metabolites result in reduced cellular differentiation. Furthermore, activation of the pseudohypoxia pathway likely promotes the growth of these neoplasias into tumors.

Original languageEnglish (US)
Pages (from-to)641-649
Number of pages9
JournalTrends in Molecular Medicine
Issue number11
StatePublished - Nov 2011

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology


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