COX7A1 enhances the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via regulating mitochondrial metabolism

Feng，Yetong1,2; Xu，Jiayi1,3,4; Shi，Mengjiao1,3,4; Liu，Rongrong1,3,4; Zhao，Lei5; Chen，Xin6; Li，Miaomiao1,7; Zhao，Yaping1,3,4; Chen，Jiahui5; Du，Wenjing8; Liu，Pengfei1,3,4,9

2022-11-01

10.1038/s41419-022-05430-3

Cell Death & Disease   影响因子和分区

2041-4889

2041-4889

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.

SCI

英语

其他

Overseas High level Talents and Intelligence Project of Xi'an City[2022JH-GCRC-0063] ; Natural Science Foundation of China["31900547","31900460"] ; Shenzhen Peacock Plan[KQTD2016113015442590]

Cell Biology

Cell Biology

WOS:000887562500003

SPRINGERNATURE

2-s2.0-85142352659

Scopus

1.National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy,The Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an,China
2.Core Research Laboratory,The Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an,China
3.International Joint Research Center on Cell Stress and Disease Diagnosis and Therapy,The Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an,China
4.Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases,The Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an,China
5.Ambulatory Surgical Center,The 2nd Clinical medical College (Shenzhen People’s Hospital) of Jinan University,The 1st Affiliated Hospital of Southern University of Science and Technology,Shenzhen,China
6.Department of Laboratory Medicine,The 2nd Clinical medical College (Shenzhen People’s Hospital) of Jinan University,The 1st Affiliated Hospitals of Southern University of Science and Technology,Shenzhen,China
7.Department of Regenerative Medicine,School of Pharmaceutical Science,Jilin University,Changchun,China
8.The Postdoctoral Research Station,School of Medicine,Nankai University,Tianjin,China
9.Key Laboratory of Environment and Genes Related To Diseases,Xi’an Jiaotong University,Ministry of Education of China,Xi’an,China

Feng，Yetong,Xu，Jiayi,Shi，Mengjiao,et al. COX7A1 enhances the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via regulating mitochondrial metabolism[J]. Cell Death & Disease,2022,13(11).

Feng，Yetong.,Xu，Jiayi.,Shi，Mengjiao.,Liu，Rongrong.,Zhao，Lei.,...&Liu，Pengfei.(2022).COX7A1 enhances the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via regulating mitochondrial metabolism.Cell Death & Disease,13(11).

Feng，Yetong,et al."COX7A1 enhances the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via regulating mitochondrial metabolism".Cell Death & Disease 13.11(2022).