Cargando…
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: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
|
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 |
_version_ | 1784835299682025472 |
---|---|
author | Feng, Yetong Xu, Jiayi Shi, Mengjiao Liu, Rongrong Zhao, Lei Chen, Xin Li, Miaomiao Zhao, Yaping Chen, Jiahui Du, Wenjing Liu, Pengfei |
author_facet | Feng, Yetong Xu, Jiayi Shi, Mengjiao Liu, Rongrong Zhao, Lei Chen, Xin Li, Miaomiao Zhao, Yaping Chen, Jiahui Du, Wenjing Liu, Pengfei |
author_sort | Feng, Yetong |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9684511 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-96845112022-11-25 COX7A1 enhances the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via regulating mitochondrial metabolism Feng, Yetong Xu, Jiayi Shi, Mengjiao Liu, Rongrong Zhao, Lei Chen, Xin Li, Miaomiao Zhao, Yaping Chen, Jiahui Du, Wenjing Liu, Pengfei Cell Death Dis Article 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. Nature Publishing Group UK 2022-11-23 /pmc/articles/PMC9684511/ /pubmed/36418320 http://dx.doi.org/10.1038/s41419-022-05430-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Feng, Yetong Xu, Jiayi Shi, Mengjiao Liu, Rongrong Zhao, Lei Chen, Xin Li, Miaomiao Zhao, Yaping Chen, Jiahui Du, Wenjing Liu, Pengfei COX7A1 enhances the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via regulating mitochondrial metabolism |
title | COX7A1 enhances the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via regulating mitochondrial metabolism |
title_full | COX7A1 enhances the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via regulating mitochondrial metabolism |
title_fullStr | COX7A1 enhances the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via regulating mitochondrial metabolism |
title_full_unstemmed | COX7A1 enhances the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via regulating mitochondrial metabolism |
title_short | COX7A1 enhances the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via regulating mitochondrial metabolism |
title_sort | cox7a1 enhances the sensitivity of human nsclc cells to cystine deprivation-induced ferroptosis via regulating mitochondrial metabolism |
topic | Article |
url | 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 |
work_keys_str_mv | AT fengyetong cox7a1enhancesthesensitivityofhumannsclccellstocystinedeprivationinducedferroptosisviaregulatingmitochondrialmetabolism AT xujiayi cox7a1enhancesthesensitivityofhumannsclccellstocystinedeprivationinducedferroptosisviaregulatingmitochondrialmetabolism AT shimengjiao cox7a1enhancesthesensitivityofhumannsclccellstocystinedeprivationinducedferroptosisviaregulatingmitochondrialmetabolism AT liurongrong cox7a1enhancesthesensitivityofhumannsclccellstocystinedeprivationinducedferroptosisviaregulatingmitochondrialmetabolism AT zhaolei cox7a1enhancesthesensitivityofhumannsclccellstocystinedeprivationinducedferroptosisviaregulatingmitochondrialmetabolism AT chenxin cox7a1enhancesthesensitivityofhumannsclccellstocystinedeprivationinducedferroptosisviaregulatingmitochondrialmetabolism AT limiaomiao cox7a1enhancesthesensitivityofhumannsclccellstocystinedeprivationinducedferroptosisviaregulatingmitochondrialmetabolism AT zhaoyaping cox7a1enhancesthesensitivityofhumannsclccellstocystinedeprivationinducedferroptosisviaregulatingmitochondrialmetabolism AT chenjiahui cox7a1enhancesthesensitivityofhumannsclccellstocystinedeprivationinducedferroptosisviaregulatingmitochondrialmetabolism AT duwenjing cox7a1enhancesthesensitivityofhumannsclccellstocystinedeprivationinducedferroptosisviaregulatingmitochondrialmetabolism AT liupengfei cox7a1enhancesthesensitivityofhumannsclccellstocystinedeprivationinducedferroptosisviaregulatingmitochondrialmetabolism |