ArticleThe Journal of biological chemistry2011
Hypoxia-induced acidosis uncouples the STIM-Orai calcium signaling complex.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Review
- Crosstalk between calcium and reactive oxygen species signaling in cancer revisited.Cell calcium · 2025Review
- Redox Enzymes P4HB and PDIA3 Interact with STIM1 to Fine-Tune Its Calcium Sensitivity and Activation.International journal of molecular sciences · 2024Article
- Vulnerability of Store-Operated Calcium Entry to Inhibitors and Microenvironment in Cells of Different Breast Cancer Subtypes.Life (Basel, Switzerland) · 2024Article
- Searching for Mechanisms Underlying the Assembly of Calcium Entry Units: The Role of Temperature and pH.International journal of molecular sciences · 2023Article
- CaInternational journal of molecular sciences · 2022Review
- Highlighting the Multifaceted Role of Orai1 N-Terminal- and Loop Regions for Proper CRAC Channel Functions.Cells · 2022Review
- Calcium entry units (CEUs): perspectives in skeletal muscle function and disease.Journal of muscle research and cell motility · 2021Article
- Lysosomal agents inhibit store-operated CaJournal of cell science · 2021Article
- Triclosan disrupts immune cell function by depressing CaToxicology and applied pharmacology · 2020Article
- Molecular Profiling for Predictors of Radiosensitivity in Patients with Breast or Head-and-Neck Cancer.Cancers · 2020Article
- Pore properties of Orai1 calcium channel dimers and their activation by the STIM1 ER calcium sensor.The Journal of biological chemistry · 2018Article
- Cross talk between increased intracellular zinc (ZnAmerican journal of physiology. Cell physiology · 2017Article
- Regulation of Orai1/STIM1 mediated IScientific reports · 2017Article
- Crosstalk between calcium and reactive oxygen species signaling in cancer.Cell calcium · 2017Review
- Article
- The Orai1 Store-operated Calcium Channel Functions as a Hexamer.The Journal of biological chemistry · 2016Article
- Identification of key amino acid residues responsible for internal and external pH sensitivity of Orai1/STIM1 channels.Scientific reports · 2015Article
- Differential Redox Regulation of Ca²⁺ Signaling and Viability in Normal and Malignant Prostate Cells.Biophysical journal · 2015Article
- Store-Operated Calcium Channels.Physiological reviews · 2015Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
The endoplasmic reticulum Ca(2+)-sensing STIM proteins mediate Ca(2+) entry signals by coupling to activate plasma membrane Orai channels. We reveal that STIM-Orai coupling is rapidly blocked by hypoxia and the ensuing decrease in cytosolic pH. In smooth muscle cells or HEK293 cells coexpressing STIM1 and Orai1, acute hypoxic conditions rapidly blocked store-operated Ca(2+) entry and the Orai1-mediated Ca(2+) release-activated Ca(2+) current (I(CRAC)). Hypoxia-induced blockade of Ca(2+) entry and I(CRAC) was reversed by NH(4)(+)-induced cytosolic alkalinization. Hypoxia and acidification both blocked I(CRAC) induced by the short STIM1 Orai-activating region. Although hypoxia induced STIM1 translocation into junctions, it did not dissociate the STIM1-Orai1 complex. However, both hypoxia and cytosolic acidosis rapidly decreased Förster resonance energy transfer (FRET) between STIM1-YFP and Orai1-CFP. Thus, although hypoxia promotes STIM1 junctional accumulation, the ensuing acidification functionally uncouples the STIM1-Orai1 complex providing an important mechanism protecting cells from Ca(2+) overload under hypoxic stress conditions.
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