ATG5 and cancer: Indeed, glycolysis in MLL–ENL–driven leukemia is augmented by inhibition of autophagy, although the underlying mechanism remains to be determined.146 Of note, enhanced lactate secretion due to the Warburg effect can change the extracellular microenvironmental pH, which in turn can activate autophagy.147 For example, in breast carcinoma cells acute acidification led to an increase in LC3 puncta together with an increase in the expression of ATG5 and BNIP3.148 Thus, degradation of essential metabolic enzymes by autophagy may impact many aspects of central metabolism in cancer.