Academic Journal
Ether phospholipids are required for mitochondrial reactive oxygen species homeostasis
| العنوان: | Ether phospholipids are required for mitochondrial reactive oxygen species homeostasis |
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| المؤلفون: | Chen, Ziheng, Ho, I-Lin, Soeung, Melinda, Yen, Er-Yen, Liu, Jintan, Yan, Liang, Rose, Johnathon L., Srinivasan, Sanjana, Jiang, Shan, Edward Chang, Q., Feng, Ningping, Gay, Jason P., Wang, Qi, Wang, Jing, Lorenzi, Philip L., Veillon, Lucas J., Wei, Bo, Weinstein, John N., Deem, Angela K., Gao, Sisi, Genovese, Giannicola, Viale, Andrea, Yao, Wantong, Lyssiotis, Costas A., Marszalek, Joseph R., Draetta, Giulio F., Ying, Haoqiang |
| المساهمون: | U.S. Department of Health & Human Services | NIH | National Cancer Institute, V Foundation for Cancer Research, UT | University of Texas MD Anderson Cancer Center, Cancer Prevention and Research Institute of Texas, Sewell Family Distinguished University Chair in Genomic Medicine |
| المصدر: | Nature Communications ; volume 14, issue 1 ; ISSN 2041-1723 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| الوصف: | Mitochondria are hubs where bioenergetics, redox homeostasis, and anabolic metabolism pathways integrate through a tightly coordinated flux of metabolites. The contributions of mitochondrial metabolism to tumor growth and therapy resistance are evident, but drugs targeting mitochondrial metabolism have repeatedly failed in the clinic. Our study in pancreatic ductal adenocarcinoma (PDAC) finds that cellular and mitochondrial lipid composition influence cancer cell sensitivity to pharmacological inhibition of electron transport chain complex I. Profiling of patient-derived PDAC models revealed that monounsaturated fatty acids (MUFAs) and MUFA-linked ether phospholipids play a critical role in maintaining ROS homeostasis. We show that ether phospholipids support mitochondrial supercomplex assembly and ROS production; accordingly, blocking de novo ether phospholipid biosynthesis sensitized PDAC cells to complex I inhibition by inducing mitochondrial ROS and lipid peroxidation. These data identify ether phospholipids as a regulator of mitochondrial redox control that contributes to the sensitivity of PDAC cells to complex I inhibition. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41467-023-37924-9 |
| الاتاحة: | http://dx.doi.org/10.1038/s41467-023-37924-9 https://www.nature.com/articles/s41467-023-37924-9.pdf https://www.nature.com/articles/s41467-023-37924-9 |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.7BADF276 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-023-37924-9 |
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