Schematic representation of how mitochondrial metabolites accumulated upon mutation of the indicated TCA cycle enzymes activate the EMT. A common pathway affected by these metabolites is the epigenetic suppression of a family of antimetastatic microRNAs, miR200, via the inhibition of histone demethylases (KDMs) and DNA demethylases (TETs). Of note, in the case of 2HG, the suppression of miR200 is indirect, and occurs via activation of Zeb1/2. See the text for more details. FH=fumarate hydratase; SDH=succinate dehydrogenase; IDH=isocitrate dehydrogenase.