NRF1 and breast carcinoma: In addition to its transcript (Supplementary Figure 6C), we observed Tfam protein was also decreased as early as 6 h after ONC201 treatment in multiple breast cancer cell lines, and it preceded that of peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC) and nuclear respiratory factor 1 (NRF1), two upstream proteins vital to mitochondrial biogenesis [44–46] (Supplementary Figure 8A, 8B, 8C, 8D).