Figure 6 from N-Myristoytransferase Inhibition Causes Mitochondrial Iron Overload and Parthanatos in TIM17A-Dependent Aggressive Lung Carcinoma
Year: 2024
Type: other
Abstract: Mitochondria are a key target of NMT inhibition in (KL/K)MUT lung carcinoma cells. A, Ultrastructure of mitochondria from (KL/K)MUT H1792 lung carcinoma cells treated with control or 1 μmol/L DDD85646 (NMTi) for the indicated times. Arrowheads, mitochondria cristae. Bar, 50 nm. B, Volcano plot of mitochondrial membrane-associated proteins whose abundance was altered by NMTi treatment. Blue lines indicate thresholds for a fold-change of two or a P value of 0.05 by moderated t test. C, Diagram of the main mitochondrial import complexes: TOM, in the outer mitochondrial membrane, and TIM23, in the inner mitochondrial membrane (IMM). TIM17A or TIM17B bind TIM23 to form the main TIM23 complex channel in the IMM. D, Kaplan–Meier curve shows percent surviving (overall survival, y-axis) over time (years, x-axis) for TCGA-LUAD (n = 501, n-event = 181). High TIM17A (Red, ≥50th percentile) were compared with low TIM17A (Blue, <50th percentile; log-rank test, P = 0.014, median OS was 3.72 years in TIM17A High vs. 4.93 in TIM17A Low). Colored shading: 95% confidence interval. E, Immunoblotting for TIM17A and TIM17B in samples from (KL/K)MUT H460 cells treated with 1 μmol/L PCLX-001 (NMTi) or vehicle control for the indicated times. Numbers, band intensity normalized to actin control. F, Immunoblotting for HSP60 and TOM20 in samples from (KL/K)MUT H460 cells treated with 1 μmol/L PCLX-001 (NMTi) or vehicle control for the indicated times. Numbers, band intensity normalized to actin.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4400980730