Figure 1. Scheme of 3-BrPA chemopotentiation induced by glutamine deprivation. SLC16A1 stabilization increases upon glutamine deprivation or L-γ-glutamyl-p-nitroanilide (GPNA)-induced inhibition of SLC1A5-mediated glutamine uptake. This event induces an enhanced 3-BrPA uptake, increases inhibition of mitochondrial complex II (mCII) and results in the generation of metabolic-oxidative stress culminating with cell death, mainly executed by autophagy. Cancer cells with a high basal level of glutamine synthetase (GLUL/GS) are able to replenish the intracellular pool of glutamine upon its withdrawal, thus bypassing 3-BrPA chemopotentiation. GLUL inhibition, achieved either pharmacologically, by methionine sulphoximine (MSO) treatment, or genetically, by overexpressing a GLUL dominant-negative form (DN-GLUL), increases SLC16A1 stability, thereby making cells sensitive to 3-BrPA chemopotentiation. Hypothetical pathways are indicated by dotted lines and squares.