The mitochondrial Ca2+ uniporter channel synergizes with fluid shear stress to induce mitochondrial Ca2+ oscillations
Abstract The mitochondrial calcium (Ca2+) uniporter (MCU) channel is responsible for mitochondrial Ca2+ influx. Its expression was found to be upregulated in endothelial cells (ECs) under cardiovascular disease conditions. Since the role of MCU in regulating cytosolic Ca2+ homeostasis in ECs exposed...
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| Format: | Article |
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Nature Portfolio
2022-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-25583-7 |
| _version_ | 1811177934405238784 |
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| author | Akshar Patel Matthew Simkulet Soumya Maity Manigandan Venkatesan Anastasios Matzavinos Muniswamy Madesh B. Rita Alevriadou |
| author_facet | Akshar Patel Matthew Simkulet Soumya Maity Manigandan Venkatesan Anastasios Matzavinos Muniswamy Madesh B. Rita Alevriadou |
| author_sort | Akshar Patel |
| collection | DOAJ |
| description | Abstract The mitochondrial calcium (Ca2+) uniporter (MCU) channel is responsible for mitochondrial Ca2+ influx. Its expression was found to be upregulated in endothelial cells (ECs) under cardiovascular disease conditions. Since the role of MCU in regulating cytosolic Ca2+ homeostasis in ECs exposed to shear stress (SS) is unknown, we studied mitochondrial Ca2+ dynamics (that is known to decode cytosolic Ca2+ signaling) in sheared ECs. To understand cause-and-effect, we ectopically expressed MCU in ECs. A higher percentage of MCU-transduced ECs exhibited mitochondrial Ca2+ transients/oscillations, and at higher frequency, under SS compared to sheared control ECs. Transients/oscillations correlated with mitochondrial reactive oxygen species (mROS) flashes and mitochondrial membrane potential (ΔΨm) flickers, and depended on activation of the mechanosensitive Piezo1 channel and the endothelial nitric oxide synthase (eNOS). A positive feedback loop composed of mitochondrial Ca2+ uptake/mROS flashes/ΔΨm flickers and endoplasmic reticulum Ca2+ release, in association with Piezo1 and eNOS, provided insights into the mechanism by which SS, under conditions of high MCU activity, may shape vascular EC energetics and function. |
| first_indexed | 2024-04-11T06:09:39Z |
| format | Article |
| id | doaj.art-60992396b0f048ee90a689948b2e1637 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T06:09:39Z |
| publishDate | 2022-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-60992396b0f048ee90a689948b2e16372022-12-22T04:41:19ZengNature PortfolioScientific Reports2045-23222022-12-0112111510.1038/s41598-022-25583-7The mitochondrial Ca2+ uniporter channel synergizes with fluid shear stress to induce mitochondrial Ca2+ oscillationsAkshar Patel0Matthew Simkulet1Soumya Maity2Manigandan Venkatesan3Anastasios Matzavinos4Muniswamy Madesh5B. Rita Alevriadou6Vascular Mechanobiology Laboratory, Department of Biomedical Engineering, and Center for Cell, Gene, and Tissue Engineering, University at Buffalo – The State University of New YorkVascular Mechanobiology Laboratory, Department of Biomedical Engineering, and Center for Cell, Gene, and Tissue Engineering, University at Buffalo – The State University of New YorkCenter for Mitochondrial Medicine, Department of Medicine, University of Texas Health San AntonioCenter for Mitochondrial Medicine, Department of Medicine, University of Texas Health San AntonioInstitute for Mathematical and Computational Engineering, Pontifical Catholic University of ChileCenter for Mitochondrial Medicine, Department of Medicine, University of Texas Health San AntonioVascular Mechanobiology Laboratory, Department of Biomedical Engineering, and Center for Cell, Gene, and Tissue Engineering, University at Buffalo – The State University of New YorkAbstract The mitochondrial calcium (Ca2+) uniporter (MCU) channel is responsible for mitochondrial Ca2+ influx. Its expression was found to be upregulated in endothelial cells (ECs) under cardiovascular disease conditions. Since the role of MCU in regulating cytosolic Ca2+ homeostasis in ECs exposed to shear stress (SS) is unknown, we studied mitochondrial Ca2+ dynamics (that is known to decode cytosolic Ca2+ signaling) in sheared ECs. To understand cause-and-effect, we ectopically expressed MCU in ECs. A higher percentage of MCU-transduced ECs exhibited mitochondrial Ca2+ transients/oscillations, and at higher frequency, under SS compared to sheared control ECs. Transients/oscillations correlated with mitochondrial reactive oxygen species (mROS) flashes and mitochondrial membrane potential (ΔΨm) flickers, and depended on activation of the mechanosensitive Piezo1 channel and the endothelial nitric oxide synthase (eNOS). A positive feedback loop composed of mitochondrial Ca2+ uptake/mROS flashes/ΔΨm flickers and endoplasmic reticulum Ca2+ release, in association with Piezo1 and eNOS, provided insights into the mechanism by which SS, under conditions of high MCU activity, may shape vascular EC energetics and function.https://doi.org/10.1038/s41598-022-25583-7 |
| spellingShingle | Akshar Patel Matthew Simkulet Soumya Maity Manigandan Venkatesan Anastasios Matzavinos Muniswamy Madesh B. Rita Alevriadou The mitochondrial Ca2+ uniporter channel synergizes with fluid shear stress to induce mitochondrial Ca2+ oscillations Scientific Reports |
| title | The mitochondrial Ca2+ uniporter channel synergizes with fluid shear stress to induce mitochondrial Ca2+ oscillations |
| title_full | The mitochondrial Ca2+ uniporter channel synergizes with fluid shear stress to induce mitochondrial Ca2+ oscillations |
| title_fullStr | The mitochondrial Ca2+ uniporter channel synergizes with fluid shear stress to induce mitochondrial Ca2+ oscillations |
| title_full_unstemmed | The mitochondrial Ca2+ uniporter channel synergizes with fluid shear stress to induce mitochondrial Ca2+ oscillations |
| title_short | The mitochondrial Ca2+ uniporter channel synergizes with fluid shear stress to induce mitochondrial Ca2+ oscillations |
| title_sort | mitochondrial ca2 uniporter channel synergizes with fluid shear stress to induce mitochondrial ca2 oscillations |
| url | https://doi.org/10.1038/s41598-022-25583-7 |
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