Genetic Screen for Cell Fitness in High or Low Oxygen Highlights Mitochondrial and Lipid Metabolism

Jain, Isha H.; Calvo, Sarah E.; Markhard, Andrew L.; Skinner, Owen S.; To, Tsz-Leung; Ast, Tslil; Mootha, Vamsi K.

doi:10.1016/j.cell.2020.03.029

Cited by 226Cancer, Hypoxia, and MetabolismRedox biology and oxidative stressMitochondrial Function and Pathology

Genetic Screen for Cell Fitness in High or Low Oxygen Highlights Mitochondrial and Lipid Metabolism

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Jain, Isha H., Calvo, Sarah E., Markhard, Andrew L., Skinner, Owen S., To, Tsz-Leung, Ast, Tslil, Mootha, Vamsi K.·2020·Cell

DOI 10.1016/j.cell.2020.03.029PMC PMC7293541

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Abstract

Human cells are able to sense and adapt to variations in oxygen levels. Historically, much research in this field has focused on hypoxia-inducible factor (HIF) signaling and reactive oxygen species (ROS). Here, we perform genome-wide CRISPR growth screens at 21%, 5%, and 1% oxygen to systematically identify gene knockouts with relative fitness defects in high oxygen (213 genes) or low oxygen (109 genes), most without known connection to HIF or ROS. Knockouts of many mitochondrial pathways thought to be essential, including complex I and enzymes in Fe-S biosynthesis, grow relatively well at low oxygen and thus are buffered by hypoxia. In contrast, in certain cell types, knockout of lipid biosynthetic and peroxisomal genes causes fitness defects only in low oxygen. Our resource nominates genetic diseases whose severity may be modulated by oxygen and links hundreds of genes to oxygen homeostasis.

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Many autophagy-related genes (WIPI2, ATG9A, ATG13, ATG14, BECN1) were common hits in the ROS and lipid peroxidation screens.
“Many autophagy-related genes were also common hits in the two screens (Fig. 2 d,e), such as WIPI2, ATG9A, ATG13, ATG14, and BECN1, suggesting an important role of autophagy in maintaining redox homeostasis in cells, as reported in previous studies31–33.”
From Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis (2021) · cites this paper as [33]
Autophagy plays an important role in maintaining redox homeostasis in cells.
“Many autophagy-related genes were also common hits in the two screens (Fig. 2 d,e), such as WIPI2, ATG9A, ATG13, ATG14, and BECN1, suggesting an important role of autophagy in maintaining redox homeostasis in cells, as reported in previous studies31–33.”
From Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis (2021) · cites this paper as [33]

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Chu, D. K., Kim, L. H.-Y., Young, P. J., Zamiri, N., Almenawer, S. A., Jaeschke, R., Szczeklik, W., Schünemann, H. J., Neary, J. D., & Alhazzani, W. (2018) · The Lancet · doi:10.1016/s0140-6736(18)30479-3 · Cited by 778 · see citing works
Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids
Kamphorst, J. J., Cross, J. R., Fan, J., de Stanchina, E., Mathew, R., White, E. P., Thompson, C. B., & Rabinowitz, J. D. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1307237110 · Cited by 726 · see citing works
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Girardis, M., Busani, S., Damiani, E., Donati, A., Rinaldi, L., Marudi, A., Morelli, A., Antonelli, M., & Singer, M. (2016) · JAMA · doi:10.1001/jama.2016.11993 · Cited by 723 · see citing works
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Imlay, J. A. (2006) · Molecular Microbiology · doi:10.1111/j.1365-2958.2006.05028.x · Cited by 717 · see citing works
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Volmer, R., van der Ploeg, K., & Ron, D. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1217611110 · Cited by 655 · see citing works
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Raymond, J., & Segrè, D. (2006) · Science · doi:10.1126/science.1118439 · Cited by 494 · see citing works
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Benita, Y., Kikuchi, H., Smith, A. D., Zhang, M. Q., Chung, D. C., & Xavier, R. J. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp425 · Cited by 469 · see citing works
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Jain, I. H., Zazzeron, L., Goli, R., Alexa, K., Schatzman-Bone, S., Dhillon, H., Goldberger, O., Peng, J., Shalem, O., Sanjana, N. E., et al. (2016) · Science · doi:10.1126/science.aad9642 · Cited by 443 · see citing works
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Chakraborty, A. A., Laukka, T., Myllykoski, M., Ringel, A. E., Booker, M. A., Tolstorukov, M. Y., Meng, Y. J., Meier, S. R., Jennings, R. B., Creech, A. L., et al. (2019) · Science · doi:10.1126/science.aaw1026 · Cited by 432 · see citing works
Squalene accumulation in cholesterol auxotrophic lymphomas prevents oxidative cell death
García‐Bermúdez, J., Baudrier, L., Bayraktar, E. C., Shen, Y., La, K., Guarecuco, R., Yücel, B., Fiore, D., Tavora, B., Freinkman, E., et al. (2019) · Nature · doi:10.1038/s41586-019-0945-5 · Cited by 424 · see citing works
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Peng, Y., Yang, Z., Zhang, H., Cui, C., Qi, X., Luo, X., Tao, X., Wu, T., Ouzhuluobu, Basang, et al. (2011) · Molecular Biology and Evolution · doi:10.1093/molbev/msq290 · Cited by 388 · see citing works
Alterations in mitochondrial membrane fluidity by lipid peroxidation products
Chen, J. J., & Yu, B. P. (1994) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(94)90167-8 · Cited by 369 · see citing works
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Xu, S., Li, S., Yang, Y., Tan, J., Lou, H., Jin, W., Yang, L., Pan, X., Wang, J., Shen, Y., et al. (2011) · Molecular Biology and Evolution · doi:10.1093/molbev/msq277 · Cited by 331 · see citing works
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Ackerman, D., Tumanov, S., Qiu, B., Michalopoulou, E., Spata, M., Azzam, A., Xie, H. J., Simon, M. C., & Kamphorst, J. J. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.08.015 · Cited by 307 · see citing works
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Arroyo, J. D., Jourdain, A. A., Calvo, S. E., Ballarano, C. A., Doench, J. G., Root, D. E., & Mootha, V. K. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.017 · Cited by 306 · see citing works
Self-citation
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Waterham, H. R., & Ebberink, M. S. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.04.006 · Cited by 283 · see citing works
Global Analysis of Plasma Lipids Identifies Liver-Derived Acylcarnitines as a Fuel Source for Brown Fat Thermogenesis
Simcox, J., Geoghegan, G., Maschek, J. A., Bensard, C. L., Pasquali, M., Miao, R., Lee, S., Jiang, L., Huck, I., Kershaw, E. E., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.006 · Cited by 277 · see citing works
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Piccolis, M., Bond, L. M., Kampmann, M., Pulimeno, P., Chitraju, C., Jayson, C. B. K., Vaites, L. P., Boland, S., Lai, Z. W., Gabriel, K. R., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.01.036 · Cited by 269 · see citing works
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Zoeller, R. A., Lake, A. C., Nagan, N., Gaposchkin, D. P., LEGNER, M. A., & Lieberthal, W. (1999) · Biochemical Journal · doi:10.1042/bj3380769 · Cited by 257 · see citing works
Mitochondrial energy generation disorders: genes, mechanisms, and clues to pathology
Frazier, A. E., Thorburn, D. R., & Compton, A. G. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.r117.809194 · Cited by 254 · see citing works
Genetic signatures of high-altitude adaptation in Tibetans
Yang, J., Jin, Z., Chen, J., Huang, X., Li, X., Liang, Y., Mao, J.-Y., Chen, X., Zheng, Z., Bakshi, A., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1617042114 · Cited by 250 · see citing works
Oxygen as a Prerequisite to the Origin of the Metazoa
NURSALL, J. R. (1959) · Nature · doi:10.1038/1831170b0 · Cited by 211 · see citing works
The protective role of plasmalogens in iron-induced lipid peroxidation
Sindelar, P. J., Guan, Z.-Z., Dallner, G., & Ernster, L. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(98)00221-4 · Cited by 181 · see citing works
Reengineering the Tumor Microenvironment to Alleviate Hypoxia and Overcome Cancer HeterogeneityPreprint
Martin, J. D., Fukumura, D., Duda, D. G., Boucher, Y., & Jain, R. K. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a027094 · Cited by 172 · see citing works
Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome
Ferrari, M., Jain, I. H., Goldberger, O., Rezoagli, E., Thoonen, R., Cheng, K., Sosnovik, D. E., Scherrer‐Crosbie, M., Mootha, V. K., & Zapol, W. M. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1621511114 · Cited by 165 · see citing works
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Ast, T., Meisel, J. D., Patra, S., Wang, H., Grange, R. M. H., Kim, S. H., Calvo, S. E., Orefice, L. L., Nagashima, F., Ichinose, F., et al. (2019) · Cell · doi:10.1016/j.cell.2019.03.045 · Cited by 156 · see citing works
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Liu, T., Tang, J.-J., Li, P., Shen, Y., Li, J., Miao, H., Li, B.-L., & Song, B. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.06.014 · Cited by 135 · see citing works
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Jain, I. H., Zazzeron, L., Goldberger, O., Marutani, E., Wojtkiewicz, G. R., Ast, T., Wang, H., Schleifer, G., Степанова, А., Brepoels, K., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.07.006 · Cited by 121 · see citing works
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Thannickal, V. J. (2009) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2008-0360ps · Cited by 116 · see citing works
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Gallego-García, A., Monera-Girona, A. J., Pajares-Martínez, E., Bastida‐Martínez, E., Pérez‐Castaño, R., Iniesta, A. A., Fontes, M., Padmanabhan, S., & Arnanz, M. E. (2019) · Science · doi:10.1126/science.aay1436 · Cited by 114 · see citing works
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Klett, E. L., Chen, S., Yechoor, A., Lih, F. B., & Coleman, R. (2017) · Journal of Lipid Research · doi:10.1194/jlr.m072512 · Cited by 106 · see citing works
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Zhu, X. G., Nicholson, S. P. V., Shen, Y., La, K., Özlü, C., Wang, T., Klompstra, D., Gültekin, Y., Chi, J., Fidelin, J., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.01.037 · Cited by 105 · see citing works
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Zoeller, R. A., Grazia, T. J., LaCamera, P. P., Park, J. O., Gaposchkin, D. P., & Farber, H. W. (2002) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00524.2001 · Cited by 97 · see citing works
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Schlüter, A., Fourcade, S., Domènech‐Estévez, E., Gabaldón, T., Huerta‐Cepas, J., Berthommier, G., Ripp, R., Wanders, R. J. A., Poch, O., & Pujol, A. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl935 · Cited by 74 · see citing works
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Ruiz, M., Ståhlman, M., Borén, J., & Pilon, M. (2019) · Journal of Lipid Research · doi:10.1194/jlr.m092494 · Cited by 69 · see citing works
Dysregulation of Plasmalogen Homeostasis Impairs Cholesterol Biosynthesis
Honsho, M., Abe, Y., & Fujiki, Y. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.656983 · Cited by 61 · see citing works
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Henze, A., & Acker, T. (2010) · Cell Cycle · doi:10.4161/cc.9.14.12249 · Cited by 61 · see citing works
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Zhou, H., & van Bokhoven, H. (2010) · Cell Cycle · doi:10.4161/cc.9.14.12591 · Cited by 59 · see citing works
A Caenorhabditis elegans model for ether lipid biosynthesis and function
Shi, X., Tarazona, P., Brock, T., Browse, J., Feußner, I., & Watts, J. L. (2015) · Journal of Lipid Research · doi:10.1194/jlr.m064808 · Cited by 59 · see citing works
Ether lipid biosynthesis: alkyl-dihydroxyacetonephosphate synthase protein deficiency leads to reduced dihydroxyacetonephosphate acyltransferase activities
de Vet, E. C. J. M., IJlst, L., Oostheim, W., Dekker, C., Moser, H. W., van den BOSCH, H., & Wanders, R. J. A. (1999) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)32423-8 · Cited by 53 · see citing works
Alterations of fatty acid metabolism and membrane fluidity in peroxisome‐defective mutant ZP102 cells
Nagura, M., Saito, M., Iwamori, M., Sakakihara, Y., & Igarashi, T. (2004) · Lipids · doi:10.1007/s11745-004-1200-z · Cited by 17 · see citing works
CRISPR /Cas9 gene editing special issue
Doench, J. G. (2016) · FEBS Journal · doi:10.1111/febs.13823 · Cited by 8 · see citing works
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Wertlake, P. T., & Winter, T. S. (1965) · New England Journal of Medicine · doi:10.1056/nejm196508192730811 · Cited by 2 · see citing works

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Soula, M., Weber, R. A., Zilka, O., Alwaseem, H., La, K., Yen, F. S., Molina, H., García‐Bermúdez, J., Pratt, D. A., & Birsoy, K. (2020) · Nature Chemical Biology · doi:10.1038/s41589-020-0613-y · Cited by 754 · see citing works
High-content CRISPR screening
Bock, C., Datlinger, P., Chardon, F. M., Coelho, M. A., Dong, M. B., Lawson, K. A., Lu, T., Maroc, L., Norman, T. M., Song, B., et al. (2022) · Nature Reviews Methods Primers · doi:10.1038/s43586-021-00093-4 · Cited by 591 · see citing works
Therapeutic targeting of the hypoxic tumour microenvironment
Singleton, D. C., Macann, A., & Wilson, W. R. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00539-4 · Cited by 493 · see citing works
Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis
Tian, R., Abarientos, A., Hong, J., Hashemi, S. H., Yan, R., Dräger, N., Leng, K., Nalls, M. A., Singleton, A. B., Xu, K., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00862-0 · Cited by 414 · see citing works
Mechanisms of mitochondrial respiratory adaptation
Bennett, C. F., Latorre‐Muro, P., & Puigserver, P. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00506-6 · Cited by 313 · see citing works
High-content CRISPR screening
Bock, C., Datlinger, P., Chardon, F. M., Coelho, M. A., Dong, M. B., Lawson, K. A., Lu, T., Maroc, L., Norman, T. M., Song, B., et al. (2022) · Nature Reviews Methods Primers · doi:10.1038/s43586-022-00098-7 · Cited by 254 · see citing works
Fatty-acid-induced FABP5/HIF-1 reprograms lipid metabolism and enhances the proliferation of liver cancer cells
Seo, J., Jeong, D., Park, J., Lee, K., Fukuda, J., & Chun, Y. (2020) · Communications Biology · doi:10.1038/s42003-020-01367-5 · Cited by 237 · see citing works
Fumarate is a terminal electron acceptor in the mammalian electron transport chain
Spinelli, J. B., Rosen, P. C., Sprenger, H.-G., Puszynska, A. M., Mann, J. L., Roessler, J. M., Cangelosi, A. L., Henne, A., Condon, K. J., Zhang, T., et al. (2021) · Science · doi:10.1126/science.abi7495 · Cited by 221 · see citing works
Peroxisomes as cellular adaptors to metabolic and environmental stress
He, A., Dean, J. M., & Lodhi, I. J. (2021) · Trends in Cell Biology · doi:10.1016/j.tcb.2021.02.005 · Cited by 186 · see citing works
Fatty acid metabolism reprogramming in ccRCC: mechanisms and potential targets
Tan, S. K., Hougen, H. Y., Merchan, J. R., Gonzalgo, M. L., & Welford, S. M. (2022) · Nature Reviews Urology · doi:10.1038/s41585-022-00654-6 · Cited by 178 · see citing works
Hypoxia and HIF-1 as key regulators of gut microbiota and host interactions
Pral, L. P., Fachi, J. L., Corrêa, R. O., Colonna, M., & Vinolo, M. A. R. (2021) · Trends in Immunology · doi:10.1016/j.it.2021.05.004 · Cited by 165 · see citing works
The Intracellular and Extracellular Microenvironment of Tumor Site: The Trigger of Stimuli‐Responsive Drug Delivery Systems
Jing, X., Hu, H., Sun, Y., Yu, B., Cong, H., & Shen, Y. (2022) · Small Methods · doi:10.1002/smtd.202101437 · Cited by 144 · see citing works
CRISPR screens in physiologic medium reveal conditionally essential genes in human cells
Rossiter, N. J., Huggler, K. S., Adelmann, C. H., Keys, H. R., Soens, R. W., Sabatini, D. M., & Cantor, J. R. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.02.005 · Cited by 133 · see citing works
Glucose Metabolic Dysfunction in Neurodegenerative Diseases—New Mechanistic Insights and the Potential of Hypoxia as a Prospective Therapy Targeting Metabolic Reprogramming
Han, R., Liang, J., & Zhou, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115887 · Cited by 125 · see citing works
Peroxisome Metabolism in Cancer
Kim, J. (2020) · Cells · doi:10.3390/cells9071692 · Cited by 123 · see citing works
Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation
Li, T., Mao, C., Wang, X., Shi, Y., & Tao, Y. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01733-5 · Cited by 125 · see citing works
Loss‐of‐Function Genetic Screening Identifies Aldolase A as an Essential Driver for Liver Cancer Cell Growth Under Hypoxia
Niu, Y., Lin, Z., Wan, A., Sun, L., Yan, S., Liang, H., Zhan, S., Chen, D., Bu, X., Liu, P., et al. (2021) · Hepatology · doi:10.1002/hep.31846 · Cited by 115 · see citing works
How protons pave the way to aggressive cancers
Swietach, P., Boedtkjer, E., & Pedersen, S. F. (2023) · Nature reviews. Cancer · doi:10.1038/s41568-023-00628-9 · Cited by 112 · see citing works
Metabolic adaptation supports enhanced macrophage efferocytosis in limited-oxygen environments
Wang, Y., Trzeciak, A. J., Rojas, W. S., Saavedra, P. H. V., Chen, Y., Chirayil, R., Etchegaray, J. I., Lucas, C. D., Puleston, D. J., Keshari, K. R., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.12.005 · Cited by 107 · see citing works
First we eat, then we do everything else: The dynamic metabolic regulation of efferocytosis
Trzeciak, A. J., Wang, Y., & Perry, J. S. A. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.08.001 · Cited by 107 · see citing works
Targeting ACSS2 with a Transition-State Mimetic Inhibits Triple-Negative Breast Cancer Growth
Miller, K. D., Pniewski, K. A., Perry, C. E., Papp, S. B., Shaffer, J. D., Velasco‐Silva, J. N., Casciano, J. C., Aramburu, T. M., Srikanth, Y. V. V., Cassel, J. A., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-20-1847 · Cited by 101 · see citing works
Mitochondrial DNA mutations in ageing and cancer
Smith, A. L. M., Whitehall, J. C., & Greaves, L. C. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13291 · Cited by 99 · see citing works
Mitochondrial fatty acid synthesis is an emergent central regulator of mammalian oxidative metabolism
Wedan, R. J., Longenecker, J. Z., & Nowinski, S. M. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.11.017 · Cited by 95 · see citing works
Dietary nutrition for neurological disease therapy: Current status and future directions
Mao, X., Yin, X., Guan, Q.-W., Xia, Q., Yang, N., Zhou, H., Liu, Z., & Jin, W. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107861 · Cited by 84 · see citing works
Cancer cells depend on environmental lipids for proliferation when electron acceptors are limited
Li, Z., Ji, B. W., Dixit, P. D., Tchourine, K., Lien, E. C., Hosios, A. M., Abbott, K. L., Rutter, J. C., Westermark, A. M., Gorodetsky, E. F., et al. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00588-8 · Cited by 81 · see citing works
Glycerolipid Synthesis and Lipid Droplet Formation in the Endoplasmic ReticulumPreprint
Farese, R. V., & Walther, T. C. (2022) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a041246 · Cited by 76 · see citing works
Turning the Oxygen Dial: Balancing the Highs and Lows
Baik, A. H., & Jain, I. H. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2020.04.005 · Cited by 69 · see citing works
Self-citation
Tumor microenvironmental nutrients, cellular responses, and cancer
Lobel, G. P., Jiang, Y., & Simon, M. C. (2023) · Cell chemical biology · doi:10.1016/j.chembiol.2023.08.011 · Cited by 74 · see citing works
Hypoxia enhances ILC3 responses through HIF-1α-dependent mechanism
Fachi, J. L., Pral, L. P., dos Santos, J. A. C., Codo, A. C., de Oliveira, S., Felipe, J. S., Zambom, F. F. F., Câmara, N. O. S., Moraes‐Vieira, P. M., Colonna, M., et al. (2021) · Mucosal Immunology · doi:10.1038/s41385-020-00371-6 · Cited by 72 · see citing works
AdipoR1 and AdipoR2 maintain membrane fluidity in most human cell types and independently of adiponectin
Ruiz, M., Ståhlman, M., Borén, J., & Pilon, M. (2019) · Journal of Lipid Research · doi:10.1194/jlr.m092494 · Cited by 69 · see citing works
Single-cell analysis reveals context-dependent, cell-level selection of mtDNA
Kotrys, A. V., Durham, T., Guo, X. A., Vantaku, V. R., Parangi, S., & Mootha, V. K. (2024) · Nature · doi:10.1038/s41586-024-07332-0 · Cited by 68 · see citing works
Self-citation
Glycine regulates lipid peroxidation promoting porcine oocyte maturation and early embryonic development
Gao, L., Zhang, C., Zheng, Y., Wu, D., Chen, X., Lan, H., Zheng, X., Wu, H., & Li, S. (2022) · Journal of Animal Science · doi:10.1093/jas/skac425 · Cited by 66 · see citing works
PEX13 prevents pexophagy by regulating ubiquitinated PEX5 and peroxisomal ROS
Demers, N. D., Riccio, V., Jo, D. S., Bhandari, S., Law, K. B., Liao, W., Kim, C., McQuibban, G. A., Choe, S., Cho, D., et al. (2022) · Autophagy · doi:10.1080/15548627.2022.2160566 · Cited by 65 · see citing works
Oxidative Stress and Reprogramming of Lipid Metabolism in Cancers
Li, S., Yuan, H., Li, L., Li, Q., Lin, P., & Li, K. (2025) · Antioxidants · doi:10.3390/antiox14020201 · Cited by 72 · see citing works
Adiponectin and Adiponectin Receptors in Atherosclerosis
Gianopoulos, I., Mantzoros, C. S., & Daskalopoulou, S. S. (2024) · Endocrine Reviews · doi:10.1210/endrev/bnae021 · Cited by 71 · see citing works
Limited oxygen in standard cell culture alters metabolism and function of differentiated cells
Tan, J., Virtue, S., Norris, D. M., Conway, O. J., Yang, M. H., Bidault, G., Gribben, C., Lugtu, F., Kamzolas, I., Krycer, J. R., et al. (2024) · The EMBO Journal · doi:10.1038/s44318-024-00084-7 · Cited by 61 · see citing works
CRISPR-Cas9 screen identifies oxidative phosphorylation as essential for cancer cell survival at low extracellular pH
Michl, J., Wang, Y., Monterisi, S., Błaszczak, W., Beveridge, R. D. D., Bridges, E., Koth, J., Bodmer, W. F., & Swietach, P. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110493 · Cited by 59 · see citing works
NADH reductive stress drives metabolic reprogramming
Yang, R., Guo, Z., & Li, B. (2025) · Trends in Cell Biology · doi:10.1016/j.tcb.2025.07.005 · Cited by 60 · see citing works
Hippocampal neurons respond to brain activity with functional hypoxia
Butt, U. J., Steixner-Kumar, A. A., Depp, C., Sun, T., Hassouna, I. A., Wüstefeld, L., Arinrad, S., Zillmann, M. R., Schopf, N., Garcia‐Agudo, L. F., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-00988-w · Cited by 53 · see citing works
Oxygen toxicity causes cyclic damage by destabilizing specific Fe-S cluster-containing protein complexes
Baik, A. H., Haribowo, A. G., Chen, X., Queliconi, B. B., Barrios, A. M., Garg, A., Maishan, M., Campos, A. R., Matthay, M. A., & Jain, I. H. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.02.013 · Cited by 55 · see citing works
Self-citation
Glutaredoxins and iron-sulfur protein biogenesis at the interface of redox biology and iron metabolism
Mühlenhoff, U., Braymer, J. J., Christ, S., Rietzschel, N., Uzarska, M. A., Weiler, B. D., & Lill, R. (2020) · Biological Chemistry · doi:10.1515/hsz-2020-0237 · Cited by 52 · see citing works
Acidosis orchestrates adaptations of energy metabolism in tumors
Groessl, S., Kalis, R., Snaebjornsson, M. T., Wambach, L., Haider, J., Andersch, F., Schulze, A., Palm, W., & Zuber, J. A. (2025) · Science · doi:10.1126/science.adp7603 · Cited by 54 · see citing works
SUMOylation-Mediated Response to Mitochondrial Stress
He, J., Cheng, J., & Wang, T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165657 · Cited by 51 · see citing works
Peroxisomal-derived ether phospholipids link nucleotides to respirasome assembly
Bennett, C. F., O’Malley, K. E., Perry, E. A., Balsa, E., Latorre‐Muro, P., Riley, C. L., Luo, C., Jedrychowski, M. P., Gygi, S. P., & Puigserver, P. (2021) · Nature Chemical Biology · doi:10.1038/s41589-021-00772-z · Cited by 49 · see citing works
Ether phospholipids are required for mitochondrial reactive oxygen species homeostasis
Chen, Z., Ho, I.-L., Soeung, M., Yen, E.-Y., Liu, J., Liang, Y., Rose, J. L., Srinivasan, S., Jiang, S., Chang, Q., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37924-9 · Cited by 49 · see citing works
Targeting Macrophage Phenotypes and Metabolism as Novel Therapeutic Approaches in Atherosclerosis and Related Cardiovascular Diseases
Wang, J., Wu, Q., Wang, X., Liu, H., Chen, M., Xu, L. N., Zhang, Z., Li, K., Li, W., & Zhong, J. (2024) · Current Atherosclerosis Reports · doi:10.1007/s11883-024-01229-z · Cited by 53 · see citing works
Molecular insights into peroxisome homeostasis and peroxisome biogenesis disorders
Fujiki, Y., Okumoto, K., Honsho, M., & Abe, Y. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2022.119330 · Cited by 47 · see citing works
Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis
Tian, R., Abarientos, A., Hong, J., Hashemi, S. H., Yan, R., Dräger, N., Leng, K., Nalls, M. A., Singleton, A. B., Xu, K., et al. (2020) · doi:10.1101/2020.06.27.175679 · Cited by 414 · see citing works
Lipoylation is dependent on the ferredoxin FDX1 and dispensable under hypoxia in human cells
Joshi, P. R., Sadre, S., Guo, X. A., McCoy, J. G., & Mootha, V. K. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.105075 · Cited by 40 · see citing works
Self-citation
Piezo-enhanced near infrared photocatalytic nanoheterojunction integrated injectable biopolymer hydrogel for anti-osteosarcoma and osteogenesis combination therapy
Xiao, C., Wang, R., Fu, R., Yu, P., Guo, J., Li, G., Wang, Z., Wang, H., Nie, J., Liu, W., et al. (2024) · Bioactive Materials · doi:10.1016/j.bioactmat.2024.01.003 · Cited by 41 · see citing works
Tumor oxygenation nanoliposome synergistic hypoxia-inducible-factor-1 inhibitor enhanced Iodine-125 seed brachytherapy for esophageal cancer
Yao, X., Lu, S., Feng, C., Suo, R., Li, H., Zhang, Y., Chen, Q., Lü, J., Wu, B., & Guo, J. (2022) · Biomaterials · doi:10.1016/j.biomaterials.2022.121801 · Cited by 39 · see citing works
Engineered stem cells by emerging biomedical stratagems
Wang, J., Zhang, X., Chen, H., Ren, H., Zhou, M., & Zhao, Y. (2024) · Science Bulletin · doi:10.1016/j.scib.2023.12.006 · Cited by 37 · see citing works
Hypoxia and intra-complex genetic suppressors rescue complex I mutants by a shared mechanism
Meisel, J. D., Miranda, M., Skinner, O. S., Wiesenthal, P. P., Wellner, S. M., Jourdain, A. A., Ruvkun, G., & Mootha, V. K. (2024) · Cell · doi:10.1016/j.cell.2023.12.010 · Cited by 37 · see citing works
Self-citation
HIF signaling: A new propellant in bone regeneration
Bai, H., Wang, Y., Zhao, Y. D., Chen, X., Xiao, Y. M., & Bao, C. (2022) · Biomaterials Advances · doi:10.1016/j.bioadv.2022.212874 · Cited by 37 · see citing works
Rewiring cell signalling pathways in pathogenic mtDNA mutations
Chung, C.-Y., Valdebenito, G. E., Chacko, A. R., & Duchen, M. R. (2021) · Trends in Cell Biology · doi:10.1016/j.tcb.2021.10.005 · Cited by 34 · see citing works
Genomic structural variation is associated with hypoxia adaptation in high-altitude zokors
An, X., Mao, L., Wang, Y., Xu, Q., Liu, X., Zhang, S., Qiao, Z., Li, B., Li, F., Kuang, Z., et al. (2024) · Nature Ecology & Evolution · doi:10.1038/s41559-023-02275-7 · Cited by 34 · see citing works
Paradigm shift: the primary function of the “Adiponectin Receptors” is to regulate cell membrane composition
Pilon, M. (2021) · Lipids in Health and Disease · doi:10.1186/s12944-021-01468-y · Cited by 33 · see citing works
Mitochondria and CancerPreprint
Kenny, T. C., & Birsoy, K. (2024) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041534 · Cited by 35 · see citing works
Hypoxia-Induced Signaling in Gut and Liver Pathobiology
Solanki, S. A., & Shah, Y. M. (2023) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-051122-094743 · Cited by 32 · see citing works
Multiplexed Imaging Mass Cytometry Analysis Characterizes the Vascular Niche in Pancreatic Cancer
Sussman, J., Kim, N., Kemp, S. B., Traum, D., Katsuda, T., Kahn, B., Xu, J., Kim, I., Eskandarian, C., Delman, D., et al. (2024) · Cancer Research · doi:10.1158/0008-5472.can-23-2352 · Cited by 32 · see citing works
Renal Lipid Metabolism Abnormalities in Obesity and Clear Cell Renal Cell Carcinoma
Bobulescu, I. A., Pop, L. M., Mani, C., Turner, K., Rivera, C., Khatoon, S., Kairamkonda, S., Hannan, R., & Palle, K. (2021) · Metabolites · doi:10.3390/metabo11090608 · Cited by 32 · see citing works
The Peroxisome-Autophagy Redox Connection: A Double-Edged Sword?
Li, H., Lismont, C., Revenco, I., Hussein, M. A. F., Costa, C. F., & Fransen, M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.814047 · Cited by 33 · see citing works
A functional analysis of 180 cancer cell lines reveals conserved intrinsic metabolic programs
Cherkaoui, S., Durot, S., Bradley, J., Critchlow, S. E., Dubuis, S., Masiero, M. M., Wegmann, R., Snijder, B., Othman, A., Bendtsen, C., et al. (2022) · Molecular Systems Biology · doi:10.15252/msb.202211033 · Cited by 32 · see citing works
Hypoxic adaptation of mitochondria and its impact on tumor cell function
Benej, M., Papandreou, I., & Denko, N. C. (2024) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2024.03.004 · Cited by 31 · see citing works
Genome-wide CRISPR/Cas9 deletion screen defines mitochondrial gene essentiality and identifies routes for tumour cell viability in hypoxia
Thomas, L. W., Esposito, C., Morgan, R., Price, S., Young, J., Williams, S. P., Maddalena, L. A., McDermott, U., & Ashcroft, M. A. (2021) · Communications Biology · doi:10.1038/s42003-021-02098-x · Cited by 31 · see citing works
Trabecular Meshwork Mitochondrial Function and Oxidative Stress
Wu, H., Shui, Y., Liu, Y., Liu, X., & Siegfried, C. J. (2021) · Ophthalmology Science · doi:10.1016/j.xops.2021.100107 · Cited by 31 · see citing works
Systems-level analyses dissociate genetic regulators of reactive oxygen species and energy production
Bennett, N. K., Lee, M., Orr, A. L., & Nakamura, K. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2307904121 · Cited by 32 · see citing works
Peroxisomes and PPARs: Emerging role as master regulators of cancer metabolism
Pratama, A. M., Sharma, M., Naidu, S., Bömmel, H. M., Prabhuswamimath, S. C., Madhusudhan, T., Wihadmadyatami, H., Bachhuka, A., & Karnati, S. (2024) · Molecular Metabolism · doi:10.1016/j.molmet.2024.102044 · Cited by 31 · see citing works
HypoxyStat, a small-molecule form of hypoxia therapy that increases oxygen-hemoglobin affinity
Blume, S. Y., Garg, A., Martí-Mateos, Y., Midha, A. D., Chew, B. T. L., Lin, B., Yu, C., Dick, R. A., Lee, P. S., Situ, E., et al. (2025) · Cell · doi:10.1016/j.cell.2025.01.029 · Cited by 29 · see citing works
Self-citation
Skeletal muscle metabolism in health and disease: Mechanisms, interventions, and clinical perspectives
Lin, D., Zhang, L., Huang, C., & Shao, W. (2026) · iScience · doi:10.1016/j.isci.2026.115024 · Cited by 31 · see citing works
Hypoxia as a medicine
Rogers, R. S., & Mootha, V. K. (2025) · Science Translational Medicine · doi:10.1126/scitranslmed.adr4049 · Cited by 28 · see citing works
Self-citation
Bcl-xL Enforces a Slow-Cycling State Necessary for Survival in the Nutrient-Deprived Microenvironment of Pancreatic Cancer
Sela, Y., Li, J., Maheswaran, S., Norgard, R. J., Yuan, S., Hubbi, M. E., Doepner, M., Xu, J. P., Ho, E. S., Mesaros, C., et al. (2022) · Cancer Research · doi:10.1158/0008-5472.can-22-0431 · Cited by 27 · see citing works
Regulation of membrane fluidity by RNF145‐triggered degradation of the lipid hydrolase ADIPOR2
Volkmar, N., Gawden‐Bone, C. M., Williamson, J. C., Nixon‐Abell, J., West, J. A., George‐Hyslop, P. S., Kaser, A., & Lehner, P. J. (2022) · The EMBO Journal · doi:10.15252/embj.2022110777 · Cited by 27 · see citing works
Sphingolipids and impaired hypoxic stress responses in Huntington disease
Burtscher, J., Pepe, G., Maharjan, N., Riguet, N., Pardo, A. D., Maglione, V., & Millet, G. P. (2023) · Progress in Lipid Research · doi:10.1016/j.plipres.2023.101224 · Cited by 27 · see citing works
Molecular Regulation of the Response of Brain Pericytes to Hypoxia
Carlsson, R., Enström, A., & Paul, G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065671 · Cited by 26 · see citing works
Tumor-intrinsic FABP5 is a novel driver for colon cancer cell growth via the HIF-1 signaling pathway
Seo, J., Yun, J.-E., Fukuda, J., & Chun, Y. (2021) · Cancer Genetics · doi:10.1016/j.cancergen.2021.11.001 · Cited by 25 · see citing works
Introducing the brain erythropoietin circle to explain adaptive brain hardware upgrade and improved performance
Ehrenreich, H., Garcia‐Agudo, L. F., Steixner-Kumar, A. A., Wilke, J. B. H., & Butt, U. J. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01551-5 · Cited by 23 · see citing works
Induction of DEPP1 by HIF Mediates Multiple Hallmarks of Ischemic Cardiomyopathy
Wyant, G. A., Jiang, Q., Singh, M., Qayyum, S., Levrero, C., Maron, B. A., & Kaelin, W. G. (2024) · Circulation · doi:10.1161/circulationaha.123.066628 · Cited by 23 · see citing works
Light-Triggered Carotenogenesis in Myxococcus xanthus: New Paradigms in Photosensory Signaling, Transduction and Gene Regulation
Padmanabhan, S., Monera-Girona, A. J., Pérez‐Castaño, R., Bastida‐Martínez, E., Pajares-Martínez, E., Bernal‐Bernal, D., Galbis-Martínez, M., Polanco, M. C., Iniesta, A. A., Fontes, M., et al. (2021) · Microorganisms · doi:10.3390/microorganisms9051067 · Cited by 23 · see citing works
Extensive transcription mis-regulation and membrane defects in AdipoR2-deficient cells challenged with saturated fatty acids
Ruiz, M., Palmgren, H., Henricsson, M., Devkota, R., Jaiswal, H., Maresca, M., Bohlooly‐Y, M., Peng, X., Borén, J., & Pilon, M. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2021.158884 · Cited by 23 · see citing works
Physiological responses to acute hypoxia in the liver of largemouth bass by alteration of mitochondrial function and Ca2+ exchange
Zhao, L., Liao, L., Yan, H., Tang, X. H., He, K., Liu, Q., Luo, J., Du, Z. J., Chen, S. Y., Zhang, X., et al. (2023) · Aquatic Toxicology · doi:10.1016/j.aquatox.2023.106436 · Cited by 21 · see citing works
Lysophospholipid acyltransferase‐mediated formation of saturated glycerophospholipids maintained cell membrane integrity for hypoxic adaptation
Li, Q., Xia, Z., Wu, Y., Ma, Y., Zhang, D., Wang, S., Fan, J., Xu, P., Li, X., Bai, L., et al. (2024) · FEBS Journal · doi:10.1111/febs.17132 · Cited by 20 · see citing works
The C. elegans PAQR-2 and IGLR-2 membrane homeostasis proteins are uniquely essential for tolerating dietary saturated fats
Devkota, R., Henricsson, M., Borén, J., & Pilon, M. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2021.158883 · Cited by 20 · see citing works
Exploiting moderate hypoxia to benefit patients with brain disease: Molecular mechanisms and translational research in progress
Ehrenreich, H., Gassmann, M., Poustka, L., Burtscher, M., Hammermann, P., Sirén, A., Nave, K., & Miskowiak, K. W. (2023) · Neuroprotection/Neuroprotection (Chichester, England. Print) · doi:10.1002/nep3.15 · Cited by 19 · see citing works
Plasmalogens and Photooxidative Stress Signaling in Myxobacteria, and How it Unmasked CarF/TMEM189 as the Δ1′-Desaturase PEDS1 for Human Plasmalogen Biosynthesis
Padmanabhan, S., Monera-Girona, A. J., Pajares-Martínez, E., Bastida‐Martínez, E., Navalón, I. D. R., Pérez‐Castaño, R., Galbis-Martínez, M., Fontes, M., & Arnanz, M. E. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.884689 · Cited by 19 · see citing works
Phenotypic screen of sixty-eight colorectal cancer cell lines identifies CEACAM6 and CEACAM5 as markers of acid resistance
Michl, J., White, B., Monterisi, S., Bodmer, W. F., & Swietach, P. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2319055121 · Cited by 19 · see citing works
JP4-039 protects chondrocytes from ferroptosis to attenuate osteoarthritis progression by promoting Pink1/Parkin-dependent mitophagy
Xie, Y., Lv, Z., Li, W., Lin, J., Sun, W. Y., Guo, H., Jin, X., Liu, Y., Jiang, R., Fei, Y., et al. (2025) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2025.01.001 · Cited by 18 · see citing works
Proteolysis-targeting chimeras in biotherapeutics: Current trends and future applications
Li, Q., Zhou, L., Qin, S., Huang, Z., Li, B., Li, B., Yang, M., Nice, E. C., Zhu, H., & Huang, C. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115447 · Cited by 17 · see citing works
Physiology: New Insights into Central Oxygen Sensing
SheikhBahaei, S. (2020) · Current Biology · doi:10.1016/j.cub.2020.06.101 · Cited by 17 · see citing works
ZEB1 induces ROS generation through directly promoting MCT4 transcription to facilitate breast cancer
Han, X., Long, Y., Duan, X., Liu, Z., Hu, X., Zhou, J., Li, N., Wang, Y., & Qin, J. (2022) · Experimental Cell Research · doi:10.1016/j.yexcr.2022.113044 · Cited by 17 · see citing works
GSTM1 suppresses cardiac fibrosis post-myocardial infarction through inhibiting lipid peroxidation and ferroptosis
Chen, K.-J., Zhang, Y., Zhu, X.-Y., Yu, S., Xie, Y., Jin, C. W., Shen, Y., Zhou, S.-Y., Dai, X.-C., Su, S., et al. (2025) · Military Medical Research · doi:10.1186/s40779-025-00610-6 · Cited by 16 · see citing works
Controlling Pericellular Oxygen Tension in Cell Culture Reveals Distinct Breast Cancer Responses to Low Oxygen Tensions
Rogers, Z. J., Colombani, T., Khan, S., Bhatt, K., Nukovic, A., Zhou, G., Woolston, B. M., Taylor, C. T., Gilkes, D. M., Slavov, N., et al. (2024) · Advanced Science · doi:10.1002/advs.202402557 · Cited by 19 · see citing works
d-cysteine impairs tumour growth by inhibiting cysteine desulfurase NFS1
Zangari, J., Stehling, O., Freibert, S., Bhattacharya, K., Rouaud, F., Serre‐Beinier, V., Maundrell, K., Montessuit, S., Ferré, S., Vartholomaiou, E., et al. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01339-1 · Cited by 22 · see citing works
Hypoxia Promotes Mitochondrial Complex I Abundance via HIF-1α in Complex III and Complex IV Deficient Cells
Saldana-Caboverde, A., Nissanka, N., García, S., Lombès, A., & Díaz, F. (2020) · Cells · doi:10.3390/cells9102197 · Cited by 17 · see citing works
Structural Variations Associated with Adaptation and Coat Color in Qinghai-Tibetan Plateau Cattle
Xia, X., Wang, F., Luo, X., Li, S., Lyu, Y., Zheng, Y., Ma, Z., Qu, K., Song, R., Liu, J., et al. (2025) · Advanced Science · doi:10.1002/advs.202503258 · Cited by 14 · see citing works
Cracking the membrane lipid code
Melero, A., & Jiménez‐Rojo, N. (2023) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2023.102203 · Cited by 14 · see citing works
Micro-/nanomotors as platforms for gas therapy
Sun, S., Liu, Y., Wang, S., Gui, Q., Liu, W., & Long, W. (2025) · Biomaterials · doi:10.1016/j.biomaterials.2025.123492 · Cited by 14 · see citing works
Peroxisomal membrane protein PMP70 confers drug resistance in colorectal cancer
Yin, J., Shao, Y., Huang, F., Hong, Y., Wei, W., Jiang, C., Zhao, Q., & Liu, L. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-07572-6 · Cited by 13 · see citing works
MYC overrides HIF-1α to regulate proliferating primary cell metabolism in hypoxia
Copeland, C. A., Olenchock, B. A., Ziehr, D. R., McGarrity, S., Leahy, K., Young, J. D., Loscalzo, J., & Oldham, W. M. (2023) · eLife · doi:10.7554/elife.82597 · Cited by 12 · see citing works

Benefits of oxygen limitation
Strzyz, P. J. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.32 · Cited by 1 · see citing works
Genetic Analysis of Hypoxia Tolerance and Susceptibility in Drosophila and Humans
Zhou, D., & Haddad, G. G. (2013) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-091212-153439 · Cited by 49 · see citing works
Whole-genome Transcriptional Responses to Hypoxia in Respiration-proficient and Respiration-deficient Yeasts
Lee, B. Y., Lee, J., Byun, J., & Woo, D. K. (2016) · Journal of Life Science
A Genome-wide CRISPR Death Screen Identifies Genes Essential for Oxidative Phosphorylation
Arroyo, J. D., Jourdain, A. A., Calvo, S. E., Ballarano, C. A., Doench, J. G., Root, D. E., & Mootha, V. K. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.017 · Cited by 306 · see citing works
Self-citation
Genome-wide CRISPR/Cas9 deletion screen defines mitochondrial gene essentiality and identifies routes for tumour cell viability in hypoxia
Thomas, L. W., Esposito, C., Morgan, R., Price, S., Young, J., Williams, S. P., Maddalena, L. A., McDermott, U., & Ashcroft, M. A. (2021) · Communications Biology · doi:10.1038/s42003-021-02098-x · Cited by 31 · see citing works

Authors: Jain, I. H., Calvo, S. E., Markhard, A. L., Skinner, O. S., To, T.-L., Ast, T., & Mootha, V. K.
Affiliations: Broad Institute (US)
Corresponding author: Mootha, Vamsi K.
ORCID: Jain, Isha H.
Calvo, Sarah E.
Skinner, Owen S.
To, Tsz-Leung
Ast, Tslil
Mootha, Vamsi K.
Venue: Cell
Publisher: Elsevier BV
Published: 2020-04
Volume: 181
Issue: 3
Pages: 716-727.e11
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2020.03.029
PMC: PMC7293541
OpenAlex: W3014660178
Semantic Scholar: f5cf6ffc17c0afcf964c1821338eea659750c183
Cited by: 224
References: 71
Citations by year: 2026: 30 · 2025: 42 · 2024: 33 · 2023: 37 · 2022: 30 · 2021: 37 · 2020: 14 · 2019: 1
FWCI: 10.09
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 394 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
Funders: National Institutes of Health (1F32GM133047-01)
J. Willard and Alice S. Marriott Foundation
U.S. Department of Energy
Howard Hughes Medical Institute
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords: oxygen homeostasis, hypoxia, cell fitness, genome-wide CRISPR screen, mitochondrial metabolism, lipid metabolism, complex I, peroxisomes, lipogenesis, hypoxia-inducible factor, reactive oxygen species
MeSH terms: Hypoxia, Genetic Testing, Humans, Lipids, Mitochondria, Oxygen, Signal Transduction, Cell Hypoxia, Reactive Oxygen Species, K562 Cells, Lipid Metabolism, Genome-Wide Association Study, HEK293 Cells, Transcriptome

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Genetic Screen for Cell Fitness in High or Low Oxygen Highlights Mitochondrial and Lipid Metabolism

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