Extended Data Fig. 2: UCP2 silencing reduces the availability of cytosolic aspartate in PDAC cell lines.
a–f, UCP2 silencing reduces the clonogenic capacity of Patu8988T and Panc1 but not those of BxPC3 and KP-2 cells. The clonogenic assays corresponding to Fig. 1f are shown (a–d). Aspartate in the medium rescues the clonogenic defect of UCP2-silenced KRASmut PDAC cells (a, b and e, f). The histogram data were referred to dox-induced CtrshRNA-transfected cells without aspartate. g, The presence of glutamate (1 mM) in the medium partially rescues the proliferation defect induced by UCP2 silencing in KRASmut PDAC cells. Doxycycline was always present in e–g. h, UCP2 silencing does not alter the expression of the mitochondrial aspartate/glutamate carrier (AGC) in PDAC cells, similar results were obtained in three biologically independent experiments. COX4 normalization was carried out on the same SDS-PAGE used to assay AGC1/2 expression levels (h). i, An oversimplification of aspartate export out of mitochondria catalysed by UCP2 or AGC in the presence or limited availability of glutamine, respectively. Values represent means ± SD of two biologically independent triplicates. Statistical significance was calculated by unpaired two-tailed Student’s t-test.
