Fig. 6: MERCs support the dialog between autophagy and OxPHOS. | Nature Communications

Fig. 6: MERCs support the dialog between autophagy and OxPHOS.

From: Autophagy regulates fatty acid availability for oxidative phosphorylation through mitochondria-endoplasmic reticulum contact sites

Fig. 6

a, b NSG mice (n = 31) were engrafted with MOLM14 cells expressing the Ctrl or VDAC1 shRNAs by intravenous injection. Seventeen days post graft, five mice shCtrl and six mice shVDAC1 were killed, and the number of human cells (hCD45+ and hCD33+) in the bone marrow and spleen was analyzed by flow cytometry. Graphs represent the number of human positive cells for hCD45 and hCD33 within the murine bone marrow and spleen from one experiment (a) (unpaired t-test). The remaining mice per group were used for overall survival analysis (b). Graph represents the Kaplan–Meier survival curves (Log-rank test). c, d NSG mice (n = 39) were engrafted with MOLM14 cells and daily treated with vehicle or IACS-010759 by gavage. Seventeen days post graft, nine mice vehicle group and 11 mice IACS-010759-treated group were killed, and the number of human cells (hCD45+ and hCD33+) in the bone marrow and spleen was analyzed by flow cytometry. Graphs represent the number of human positive cells for hCD45 and hCD33 within the murine bone marrow and spleen (c) (unpaired t-test). The remaining mice were used for overall survival analysis (d). Graph represents the Kaplan–Meier survival curves (Log-rank test). e–g Viable bone marrow AML blasts from mice treated with IACS-010759 were stained for Bodipy 493/503 and DAPI. Scale bar: 10 µm (e). Histograms show the number or the area of Bodipy 493/503 dots per cell (f, g) (unpaired t-test). h Viable bone marrow AML blasts from mice treated with IACS-010759 (one experiment) were subjected to Western blot analysis for actin and LC3B. Numbers indicate ratios obtained by densitometric analysis. i Purified viable bone marrow AML blasts from mice treated with IACS-010759 (one experiment) were subjected to PLA assay. Numbers represent the number of PLA dots per cell (minimum 130 cells, unpaired t-test). Scale bar: 10 µm (j). Schematic diagram depicting the interplay between the autophagy process and the mitochondria in AML cells. Autophagy appears as a major regulator of mitochondria activity with the mitochondria controlling its supply of FFAs by regulating the number of autophagosomes via the formation MERCs. Data are means ± s.e.m.

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