Fig. 5: ApoA1-enforced lipid remodeling reduces 7-ketocholesterol impairment of TAM mitochondrial translation. | Nature Communications

Fig. 5: ApoA1-enforced lipid remodeling reduces 7-ketocholesterol impairment of TAM mitochondrial translation.

From: Oncolytic viruses engineered to enforce cholesterol efflux restore tumor-associated macrophage phagocytosis and anti-tumor immunity in glioblastoma

Fig. 5

Volcano plot (a), lipid metabolism-related pathway (b), and sterol metabolism heatmap (c) of differentially expressed genes of between Puro-TAMs and APOA1-TAMs. n = 3 biological samples per group. Heatmap (d) and quantification (e) of cholesterol-targeted metabolomics between Puro-TAMs and APOA1-TAMs. n = 4 biological samples per group. f Schematic molecular structure of cholesterol oxidation to 7-ketocholesterol (7K-Cho) and 24(S),25-epoxy-cholesterol (Epoxy-Cho). g Heatmap of differentially expressed mitochondrial RNA metabolism genes between Puro-TAMs and APOA1-TAMs. h Representative TME images of mitochondria of TAMs. Arrows indicate small mitochondria with less content. The images are representative of 2 samples per group. i qPCR analysis of mitochondrial RNA metabolism genes. n = 2 independent experiments. Quantification of cytoplasmic and mitochondrial proteins (j) and mitochondrial activity (k) in cholesterol-treated BMDMs. Protein, n = 3 biological samples per group. MitoTracker, n = 5 biological samples per group. l Representative Coomassie staining of SDS–PAGE gel of cytoplasmic protein and mitochondrial protein of BMDMs. n = 5 independent experiments. m Representative TME images of 7K-Cho-treated cell-free mitochondria and quantification of the number holes in mitochondria. Arrows show mitochondria with holes or loss of contents. The number of holes per mitochondria within a TEM image of a 1 µm size field of view was quantified. The images are representative of 3 samples. n Representative flow plots of the mitochondrial membrane potential of BMDMs. n = 2 biological samples per group. o Representative silver staining and quantification of SDS–PAGE gels of mitochondrial proteins in Puro-TAMs and APOA1-TAMs. n = 2 biological samples per group. p Quantification of ex vivo phagocytosis in ApoA1- and 7K-Cho-treated TAMs. n = 5 biological samples per group. Statistical significance was determined using the unpaired t test (Two-tailed) in j, k, l, m, p. All data are the mean ± SD. Source data are provided in the Source Data file.

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