Fig. 8: The combination of HPA-12 and Creno activates mitophagy in AML cells. | Nature Communications

Fig. 8: The combination of HPA-12 and Creno activates mitophagy in AML cells.

From: Targeting ceramide transfer protein sensitizes AML to FLT3 inhibitors via a GRP78-ATF6-CHOP axis

Fig. 8

a, b Transmission electron microscopy images of morphological changes in organelles in MV4-11 cells in the DMSO and Combo groups. The cells were treated with HPA-12 (80 µM) or Creno (6 µM) for 48 h. Red arrows indicate mitochondria. Blue arrows indicate autophagosomes engulfing damaged mitochondrial structures. Scale bar, 2 μm. c Confocal microscopy of treated MV4-11 cells dual labeled with an anti-LC3B antibody (red) and the mitochondrial marker Tom20 (green). One field per slide and three slides per group were used for image analysis with ZEN and subsequent statistical analysis. n = 5 independent experiments. Scale bar, 10 μm. d Expression of Atg7 and P62 in MV4-11 cells. e Effect of the autophagy inhibitor CQ on the viability of MV4-11 cells. The cells were treated with DMSO, HPA-12 (80 µM), Creno (6 µM) or their combination for 24 h prior to the viability assay. CQ (10 µM) was added for 24 h of treatment with the other drugs. n = 3 independent experiments. f, g Effects of the mitophagy inhibitor Mdivi-1 on the viability of MV4-11 cells. The cells were treated with DMSO, HPA-12 (80 µM), Creno (6 µM) or their combination for 48 h prior to the viability assay. Mdivi-1 (10 µM) was added for 48 h of treatment with other drugs. n = 3 independent experiments. The data are presented as the means ± SDs, and differences were compared by 2-tailed Student’s t tests. Multiple groups were analyzed with one-way ANOVA. **P < 0.01; ***P < 0.001. Source data are provided as a source data file.

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