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COX7A1 enhances the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via regulating mitochondrial metabolism
COX7A1, a subunit of cytochrome c oxidase, holds an important position in the super-assembly which integrates into multi-unit heteromeric complexes peripherally in the mitochondrial electron transport chain (ETC). Recently, some studies indicated the significant potential of COX7A1 in cancer metabol...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9684511/ https://www.ncbi.nlm.nih.gov/pubmed/36418320 http://dx.doi.org/10.1038/s41419-022-05430-3 |
Sumario: | COX7A1, a subunit of cytochrome c oxidase, holds an important position in the super-assembly which integrates into multi-unit heteromeric complexes peripherally in the mitochondrial electron transport chain (ETC). Recently, some studies indicated the significant potential of COX7A1 in cancer metabolism and therapy. However, the underlying metabolic process and therapy mechanism remain unclear. In this study, COX7A1-overexpressed cell line was established via lentivirus transduction. The relationship between COX7A1 and ferroptosis, a novel form of cell death driven by iron-dependent lipid peroxidation, was further analyzed in different human non-small-cell lung carcinoma (NSCLC) cells respectively. Our results showed that COX7A1 increased the sensitivity of NSCLC cells to the ferroptosis induced by cysteine deprivation via enhancing the tricarboxylic acid (TCA) cycle and the activity of complex IV in mitochondrial ETC. Meanwhile, COX7A1 suppressed mitochondrial dynamics as well as mitochondrial biogenesis and mitophagy through blocking autophagic flux. The autophagy activator, rapamycin, relieved the autophagic blockage and further strengthened the sensitivity to cysteine deprivation-induced ferroptosis of NSCLC cells in vitro and in vivo. Taken together, our data indicate the close association of COX7A1 with cysteine deprivation-induced ferroptosis, and provide a novel insight into the therapy mode against human NSCLC. |
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