Fig. 5: Increased mitophagy in persister cells.
From: Early tolerance and late persistence as alternative drug responses in cancer
a Gene ontology analysis performed in persisters on differentially expressed genes common among the two treatments. The pathways related to mitochondria functions are reported, ranked by -LOG10(p-value). b UMAP embedding derived from scRNA-seq analysis highlighting the increased expression of a mitophagy signature in the persister population. c Mitochondrial mass measured in persisters by performing a mitochondrial green fluorescent assay. The Median Fluorescent Intensity (MFI) is reported for each treatment of one representative experiment. d Mitochondrial number, normalized to the cytosolic fraction occupied by mitochondria (n = 25 fields; median; whiskers: min to max; 25th and 75th percentiles are shown). Significant differences among groups were measured by an ANOVA followed by Dunnett’s post-test (****P < 0.0001). Representative images from Transmitted Electron Microscopy (TEM) (scale bar 1 µm) (e) to calculate mitochondria circularity (f). Significant differences among groups were measured by an ANOVA followed by Dunnett’s post-test (n = 25 fields; median; whiskers: min to max; 25th and 75th percentiles are shown) (****P < 0.0001). g Representative images of mitophagy from TEM in persisters after bafilomycin treatment. Asterisks indicate mitophagy events. Scale bar: 500 nm. h. Mitophagic flux measured as relative fluorescence intensity (RFI) by mt-mKeima reporter in HCT116 cells infected to silence PINK1 or a SCR control during FOLFOX or FOLFIRI treatment. Significant differences among groups were calculated by applying one-way ANOVA followed by Sidak’s post-test for multiple comparisons (n = 3; mean ± SEM) (****P < 0.0001; **P = 0.0049). Source data are provided as a Source Data file.
