Revisiting the TCA Cycle: Signaling to Tumor Formation

Overview

Journal Trends Mol Med

Specialties General Medicine
Molecular Biology

Date 2011 Jul 19

PMID 21764377

Citations 118

Authors

Nuno Raimundo

Bora E Baysal

Gerald S Shadel

Affiliations

Soon will be listed here.

Abstract

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.

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