Figure 8 from N-Myristoytransferase Inhibition Causes Mitochondrial Iron Overload and Parthanatos in TIM17A-Dependent Aggressive Lung Carcinoma
Year: 2024
Type: other
Abstract: Genetic targeting of TIM17A causes mitochondrial ferrous iron accumulation and activation of parthanatos in (KL/K)MUT lung carcinoma cells. A, Mitochondrial ferrous iron detection in (KL/K)MUT and (KL/K)WT cells transfected with non-targeting control or two different TIM17A siRNAs. Quantification of signal intensity on a representative experiment out of two using randomly imaged fields containing at least 480 cells per experimental condition. Graph bars, group mean; error bars, SEM. a.u., arbitrary units. *, P = 0.0101 for control vs. #1, P = 0.0131 for control vs. #2; ns = not significant (Student t test). Representative microscope images are shown. Arrowheads, Mito-FerroGreen positive cells. Bars, 15 μm. Bottom, TIM17A immunoblotting in lysates from the cells used above. Numbers: band intensity normalized to actin control. B, Protein PARylation detection by immunoblotting in H1792 cells transfected with non-targeting control and two different TIM17A oligos for 72 hours. Numbers: band intensity normalized to actin control. C, H460 cells stably expressing a Tet-inducible TIM17A shRNA treated or not with Dox were stained with p-H2A.X and DAPI. Arrowheads, nuclei containing p-H2A.X-positive foci. Bar, 10 μm. D, AIF subcellular localization in (KL/K)MUT H460 cells stably expressing a Tet-inducible TIM17A shRNA treated or not with Dox. Cytoplasmic and nuclear lysates were separated and immunoblotted for AIF. Tubulin, TOM20, and lamin staining were used to verify fraction purity. Numbers: nuclear AIF band intensity normalized to lamin A/B. E, Summary of our findings reporting that myristoylation inhibition induces parthanatos through loss of TIM17A and mitochondrial ferrous iron overload in (KL/K)MUT lung carcinoma.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4401117347