Extended Data Fig. 7: Basis of IMT-induced cellular toxicity.
From: Small-molecule inhibitors of human mitochondrial DNA transcription
a, ROS levels after IMT1 treatment in A2780 cells were determined using the Cellular ROS assay kit Orange (mean ± s.e.m., n = 5 biological replicates). b, Immunoblot analysis of the apoptosis marker cleaved PARP. A2780 cells were treated with IMT1 for the indicated time points and collected by trypsin treatment (attached). For later time points, cell culture supernatants were collected and detached or dead cells were isolated by centrifugation (supernatant) (20 μg per lane). A representative image of n = 3 independent experiments is shown. c, Heat maps illustrating the fold-change in protein levels in apoptosis (top, left), one-carbon pathway (bottom, left), degradation and stress response (right). d, Overview of changes in central carbon metabolism after IMT1 treatment. Changes in metabolite levels are given as fold of control at the indicated time points. Dark blue, minimum (0); dark red, maximum (2). e, Immunoblot analysis of the proliferation marker PCNA. A2780 cells were treated with IMT1B (+) or DMSO (−) for the indicated time points (20 μg per lane). A representative image of n = 2 independent experiments is shown.
