Oxygen and mammalian cell culture: are we repeating the experiment of Dr. Ox?

Hypoxia-inducible factors in physiology and medicine

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Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1α during hypoxia

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Defining normoxia, physoxia and hypoxia in tumours—implications for treatment response

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Iron‐sulphur clusters and the problem with oxygen

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Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids

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Hypoxia as a therapy for mitochondrial disease

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Histone demethylase KDM6A directly senses oxygen to control chromatin and cell fate

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Low oxygen concentration extends the lifespan of cultured human diploid cells

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Hypoxia induces rapid changes to histone methylation and reprograms chromatin

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Nox4: A Hydrogen Peroxide-Generating Oxygen Sensor

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Cellular Adaptation to Hypoxia through Hypoxia Inducible Factors and beyond

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The metabolic roots of senescence: mechanisms and opportunities for intervention

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

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Metabolic Reprogramming of Cancer Cells during Tumor Progression and Metastasis

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Fumarate is a terminal electron acceptor in the mammalian electron transport chain

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Mitochondrial lactate metabolism: history and implications for exercise and disease

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Tumor Hypoxia as a Barrier in Cancer Therapy: Why Levels Matter

Hompland, T., Fjeldbo, C. S., & Lyng, H. (2021) · Cancers · doi:10.3390/cancers13030499 · Cited by 186

Physiological hypoxia restrains the senescence-associated secretory phenotype via AMPK-mediated mTOR suppression

van Vliet, T., Varela-Eirin, M., Wang, B., Borghesan, M., Brandenburg, S. M., Franzin, R., Evangelou, K., Seelen, M., Gorgoulis, V., & Demaria, M. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.03.018 · Cited by 172

Metabolic regulation of skeletal cell fate and function in physiology and disease

van Gastel, N., & Carmeliet, G. (2021) · Nature Metabolism · doi:10.1038/s42255-020-00321-3 · Cited by 134

Energy metabolism in mammalian sperm motility

Amaral, A. (2022) · WIREs Mechanisms of Disease · doi:10.1002/wsbm.1569 · Cited by 123

Respiratory Supercomplexes Promote Mitochondrial Efficiency and Growth in Severely Hypoxic Pancreatic Cancer

Hollinshead, K. E. R., Parker, S. J., Eapen, V. V., Encarnación-Rosado, J., Sohn, A. S. W., Oncu, T., Cammer, M., Mancias, J. D., & Kimmelman, A. C. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108231 · Cited by 118

The Rise of Physiologic Media

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The effect of extracellular vesicles on the regulation of mitochondria under hypoxia

Zhang, Y., Tan, J., Miao, Y., & Zhang, Q. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03640-9 · Cited by 92

The brain–body energy conservation model of aging

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Establishment of physiologically relevant oxygen gradients in microfluidic organ chips

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Hypoxia preconditioned bone marrow-derived mesenchymal stromal/stem cells enhance myoblast fusion and skeletal muscle regeneration

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Limited oxygen in standard cell culture alters metabolism and function of differentiated cells

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The polar oxy-metabolome reveals the 4-hydroxymandelate CoQ10 synthesis pathway

Banh, R. S., Kim, E. S., Spillier, Q., Biancur, D. E., Yamamoto, K., Sohn, A. S. W., Shi, G., Jones, D. R., Kimmelman, A. C., & Pacold, M. E. (2021) · Nature · doi:10.1038/s41586-021-03865-w · Cited by 59

In Vitro Oxygen Glucose Deprivation Model of Ischemic Stroke: A Proteomics-Driven Systems Biological Perspective

Babu, M., Singh, N., & Datta, A. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-02745-2 · Cited by 61

Standardizing designed and emergent quantitative features in microphysiological systems

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Metabolism-driven chromatin dynamics: Molecular principles and technological advances

Sahu, V., & Lü, C. (2025) · Molecular Cell · doi:10.1016/j.molcel.2024.12.012 · Cited by 56

Oncogenic IDH mutations increase heterochromatin-related replication stress without impacting homologous recombination

Schvartzman, J. M., Forsyth, G., Walch, H. S., Chatila, W. K., Taglialatela, A., Lee, B. J., Zhu, X., Gershik, S., Cimino, F. V., Santella, A., et al. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.05.026 · Cited by 53

A prevalent neglect of environmental control in mammalian cell culture calls for best practices

Klein, S. G., Alsolami, S. M., Steckbauer, A., Arossa, S., Parry, A. J., Ramos‐Mandujano, G., Alsayegh, K. N., Belmonte, J. C. I., Li, M., & Duarte, C. M. (2021) · Nature Biomedical Engineering · doi:10.1038/s41551-021-00775-0 · Cited by 45

Tumor collection/processing under physioxia uncovers highly relevant signaling networks and drug sensitivity

Kumar, B., Adebayo, A. K., Prasad, M. S., Capitano, M. L., Wang, R., Bhat‐Nakshatri, P., Anjanappa, M., Simpson, E. R., Chen, D., Liu, Y., et al. (2022) · Science Advances · doi:10.1126/sciadv.abh3375 · Cited by 45

An In Vitro and In Vivo Study of the Efficacy and Toxicity of Plant-Extract-Derived Silver Nanoparticles

Desai, A. S., Singh, A., Edis, Z., Bloukh, S. H., Shah, P., Pandey, B., Agrawal, N., & Bhagat, N. (2022) · Journal of Functional Biomaterials · doi:10.3390/jfb13020054 · Cited by 44

Bioengineering the Oxygen-Deprived Tumor Microenvironment Within a Three-Dimensional Platform for Studying Tumor-Immune Interactions

Bhattacharya, S., Calar, K., Evans, C. M., Petrasko, M., & de la Puente, P. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.01040 · Cited by 39

Directed evolution of LaccID for cell surface proximity labeling and electron microscopy

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A Histone Methylation–MAPK Signaling Axis Drives Durable Epithelial–Mesenchymal Transition in Hypoxic Pancreatic Cancer

Brown, B. A., Myers, P. J., Adair, S. J., Pitarresi, J. R., Sah‐Teli, S. K., Campbell, L. A., Hart, W. S., Barbeau, M. C., Leong, K. M., Seyler, N. M., et al. (2024) · Cancer Research · doi:10.1158/0008-5472.can-22-2945 · Cited by 40

In situ monitoring reveals cellular environmental instabilities in human pluripotent stem cell culture

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Relevance of the Warburg Effect in Tuberculosis for Host-Directed Therapy

Cumming, B. M., Pacl, H. T., & Steyn, A. J. C. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.576596 · Cited by 31

Metabolomics in oncology

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Sulfide oxidation promotes hypoxic angiogenesis and neovascularization

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A New Non-invasive Technique for Measuring 3D-Oxygen Gradients in Wells During Mammalian Cell Culture

Silva, C. J. P., Liebsch, G., Meier, R. J., Gutbrod, M. S., Balmayor, E. R., & van Griensven, M. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00595 · Cited by 32

HYPOXIA AND REPRODUCTIVE HEALTH: Hypoxic regulation of preimplantation embryos: lessons from human embryonic stem cells

Houghton, F. D. (2020) · Reproduction · doi:10.1530/rep-20-0322 · Cited by 31

Raman based chemometric model development for glycation and glycosylation real time monitoring in a manufacturing scale CHO cell bioreactor process

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Succinate metabolism in the retinal pigment epithelium uncouples respiration from ATP synthesis

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Impact of sodium glucose linked cotransporter‐2 inhibition on renal microvascular oxygen tension in a rodent model of diabetes mellitus

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The Art of Inducing Hypoxia

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The bioactivity of neuronal-derived nitric oxide in aging and neurodegeneration: Switching signaling to degeneration

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Circumventing the Crabtree effect in cell culture: A systematic review

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Factors implicating the validity and interpretation of mechanobiology studies in simulated microgravity environments

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Whole-Body and Whole-Organ 3D Imaging of Hypoxia Using an Activatable Covalent Fluorescent Probe Compatible with Tissue Clearing

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Hypoxic preconditioning-engineered bone marrow mesenchymal stem cell-derived exosomes promote muscle satellite cell activation and skeletal muscle regeneration via the miR-210-3p/KLF7 mechanism

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Toward Best Practices for Controlling Mammalian Cell Culture Environments

Klein, S. G., Steckbauer, A., Alsolami, S. M., Arossa, S., Parry, A. J., Li, M., & Duarte, C. M. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.788808 · Cited by 23

The Warburg Effect Reinterpreted 100 yr on: A First-Principles Stoichiometric Analysis and Interpretation from the Perspective of ATP Metabolism in Cancer Cells

Nath, S., & Balling, R. (2024) · Function · doi:10.1093/function/zqae008 · Cited by 23

Metabolic adaptations in cancer progression

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Comprehensive Metabolic Profiling of MYC-Amplified Medulloblastoma Tumors Reveals Key Dependencies on Amino Acid, Tricarboxylic Acid and Hexosamine Pathways

Pham, K., Hanaford, A. R., Poore, B., Maxwell, M. J., Sweeney, H., Parthasarathy, A., Alt, J., Rais, R., Slusher, B. S., Eberhart, C. G., et al. (2022) · Cancers · doi:10.3390/cancers14051311 · Cited by 21

Origins and molecular effects of hypoxia in cancer

Rey-Keim, S., & Schito, L. (2024) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2024.10.001 · Cited by 22

Recent Advances in Understanding the Human Fungal Pathogen Hypoxia Response in Disease Progression

Puerner, C. T. S., Vellanki, S., Strauch, J. L., & Cramer, R. A. (2023) · Annual Review of Microbiology · doi:10.1146/annurev-micro-032521-021745 · Cited by 21

Calcium (Ca2+) fluxes at mitochondria-ER contact sites (MERCS) are a new target of senolysis in therapy-induced senescence (TIS)

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Redefining the role of hypoxia-inducible factors (HIFs) in oxygen homeostasis

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Gas regulation of complex II reversal via electron shunting to fumarate in the mammalian ETC

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Nano-Electrochemical Characterization of a 3D Bioprinted Cervical Tumor Model

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Mitochondrial uncoupling proteins protect human airway epithelial ciliated cells from oxidative damage

Jain, A., Kim, B. R., Yu, W., Moninger, T. O., Karp, P. H., Wagner, B. A., & Welsh, M. J. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2318771121 · Cited by 20

Pathogenic Fungal Sensing and Responses to Stressful Host Environments

Rapala, J. R., Anderson, F. M., Larkin, A., & O’Meara, T. R. (2025) · Annual Review of Microbiology · doi:10.1146/annurev-micro-051024-033116 · Cited by 17

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 20

Conditional lethality profiling reveals anticancer mechanisms of action and drug-nutrient interactions

Flickinger, K. M., Wilson, K. M., Rossiter, N. J., Hunger, A. L., Vishwasrao, P., Lee, T. D., Fritz, C. M., Richards, R. M., Hall, M. D., & Cantor, J. R. (2024) · Science Advances · doi:10.1126/sciadv.adq3591 · Cited by 18

Systematic alteration of in vitro metabolic environments reveals empirical growth relationships in cancer cell phenotypes

Kochanowski, K., Sander, T., Link, H., Chang, J. B., Altschuler, S. J., & Wu, L. F. (2021) · Cell Reports · doi:10.1016/j.celrep.2020.108647 · Cited by 16

Cultivation of human skin cells under physiological oxygen concentration modulates expression of skin significant genes and response to hydroxy acids

Lee, K., Kim, D., & Kim, W. (2021) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2021.02.113 · Cited by 14

Ten “Cheat Codes” for Measuring Oxidative Stress in Humans

Cobley, J. N., Margaritelis, N. V., Chatzinikolaou, P. N., Nikolaidis, M. G., & Davison, G. W. (2024) · Antioxidants · doi:10.3390/antiox13070877 · Cited by 17

Reflections on the Biology of Cell Culture Models: Living on the Edge of Oxidative Metabolism in Cancer Cells

Morán-Álvarez, A., González‐Menéndez, P., Mayo, J. C., & Sainz, R. M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032717 · Cited by 13

Molecular and Functional Characteristics of Airway Epithelium under Chronic Hypoxia

Wong, S. L., Kardia, E., Vijayan, A., Umashankar, B., Pandžić, E., Zhong, L., Jaffé, A., & Waters, S. A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076475 · Cited by 11

Hyperoxia Reprogrammes Microvascular Endothelial Cell Response to Hypoxia in an Organ-Specific Manner

Reiterer, M., Eakin, A., Burke, A., Johnson, R. S., & Branco, C. M. (2022) · Cells · doi:10.3390/cells11162469 · Cited by 11

The Goldilocks Oxygen Principle: not too little and not too much

Flanigan, W., & Jain, I. H. (2022) · Nature Cardiovascular Research · doi:10.1038/s44161-022-00178-7 · Cited by 10

In vitro temporal HIF‐mediated deposition of osteochondrogenic matrix governed by hypoxia and osteogenic factors synergy

Calejo, I., Costa‐Almeida, R., Reis, R. L., & Gomes, M. E. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.30138 · Cited by 11

Oxygen control in cell culture – Your cells may not be experiencing what you think!

Rogers, Z. J., Flood, D., Bencherif, S. A., & Taylor, C. T. (2024) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2024.11.036 · Cited by 13

A genetically encoded system for oxygen generation in living cells

Markhard, A. L., McCoy, J. G., To, T., & Mootha, V. K. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2207955119 · Cited by 10

Modeling Preclinical Cancer Studies under Physioxia to Enhance Clinical Translation

Adebayo, A. K., & Nakshatri, H. (2022) · Cancer Research · doi:10.1158/0008-5472.can-22-2311 · Cited by 12

Identification of the Cysteine Protease Legumain as a Potential Chronic Hypoxia-Specific Multiple Myeloma Target Gene

Clees, A.-S., Stolp, V., Häupl, B., Fuhrmann, D. C., Wempe, F., Seibert, M., Weber, S., Banning, A., Tikkanen, R., Williams, R. D., et al. (2022) · Cells · doi:10.3390/cells11020292 · Cited by 9

The oxygen level in air directs airway epithelial cell differentiation by controlling mitochondrial citrate export

Kim, B. R., Rauckhorst, A. J., Chimenti, M. S., Rehman, T., Keen, H. L., Karp, P. H., Taylor, E. B., & Welsh, M. J. (2025) · Science Advances · doi:10.1126/sciadv.adr2282 · Cited by 9

Perichondrium-inspired permeable nanofibrous tube well promoting differentiation of hiPSC-derived pellet toward hyaline-like cartilage pellet

Lee, S. J., Nam, Y., Rim, Y. A., Lee, K.-J., Ju, J. H., & Kim, D. S. (2021) · Biofabrication · doi:10.1088/1758-5090/ac1e76 · Cited by 8

Evaluation of in vitro coculture of keratinocytes derived from foreskin and adipose‐derived mesenchymal stem cells (AMSCs) on a multilayer oxygen‐releasing electrospun scaffold based on PU/PCL.Sodium percarbonate (SPC)‐gelatine/PU

Azari, A., Rahimi, A., Rajabibazl, M., Abbaszadeh, H., Hosseinzadeh, S., & Rahimpour, A. (2023) · Cell Biochemistry and Function · doi:10.1002/cbf.3793 · Cited by 7

TERT Promoter Methylation Is Oxygen-Sensitive and Regulates Telomerase Activity

Doğan, F., & Forsyth, N. R. (2024) · Biomolecules · doi:10.3390/biom14010131 · Cited by 7

Bioenergetics of simultaneous oxygen and nitrate respiration and nitric oxide production in a Pseudomonas aeruginosa agar colony biofilm

Stoodley, P., Toelke, N., Schwermer, C. U., & de Beer, D. (2024) · Biofilm · doi:10.1016/j.bioflm.2024.100181 · Cited by 7

The oxygen sensor prolyl hydroxylase domain 2 regulates the in vivo suppressive capacity of regulatory T cells

Ajouaou, Y., Azouz, A., Taquin, A., Denanglaire, S., Hussein, H., Krayem, M., Andris, F., Moser, M., Goriely, S., & Léo, O. (2022) · eLife · doi:10.7554/elife.70555 · Cited by 6

Rust and redemption: iron–sulfur clusters and oxygen in human disease and health

Egozi, S., & Ast, T. (2025) · Metallomics · doi:10.1093/mtomcs/mfaf022 · Cited by 6

Oxygen tension influences embryonic stem cell maintenance and has lineage specific effects on neural and cardiac differentiation

Mennen, R. H., de Leeuw, V. C., & Piersma, A. H. (2020) · Differentiation · doi:10.1016/j.diff.2020.07.001 · Cited by 7

Developmental ability of Hanwoo muscle satellite cells under culture conditions mimicking the in vivo environment

Park, G., Park, S., Oh, S., Lee, S.-H., & Choi, J. (2024) · Frontiers in Sustainable Food Systems · doi:10.3389/fsufs.2024.1399801 · Cited by 5

Emerging Trends for the Regulation of Thiol-Based Redox Transcription Factor Pathways

Parkies, S. L., Lind, D. J., & Pillay, C. S. (2025) · Biochemistry · doi:10.1021/acs.biochem.5c00268 · Cited by 5

Hypoxia Modulates Regenerative Potential of Fetal Stem Cells

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Insights into PINK1/Parkin function and dysfunction from Drosophila models

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