Are Multiple Mitochondrial Related Signalling Pathways Involved in Carotid Body Oxygen Sensing?
It is generally acknowledged that the carotid body (CB) type I cell mitochondria are unique, being inhibited by relatively small falls in PaO2 well above those known to inhibit electron transport in other cell types. This feature is suggested to allow for the CB to function as an acute O2 sensor, be...
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| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2022.908617/full |
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| author | Andrew P. Holmes Agnieszka Swiderska Demitris Nathanael Hayyaf S. Aldossary Hayyaf S. Aldossary Clare J. Ray Andrew M. Coney Prem Kumar |
| author_facet | Andrew P. Holmes Agnieszka Swiderska Demitris Nathanael Hayyaf S. Aldossary Hayyaf S. Aldossary Clare J. Ray Andrew M. Coney Prem Kumar |
| author_sort | Andrew P. Holmes |
| collection | DOAJ |
| description | It is generally acknowledged that the carotid body (CB) type I cell mitochondria are unique, being inhibited by relatively small falls in PaO2 well above those known to inhibit electron transport in other cell types. This feature is suggested to allow for the CB to function as an acute O2 sensor, being stimulated and activating systemic protective reflexes before the metabolism of other cells becomes compromised. What is less clear is precisely how a fall in mitochondrial activity links to type I cell depolarisation, a process that is required for initiation of the chemotransduction cascade and post-synaptic action potential generation. Multiple mitochondrial/metabolic signalling mechanisms have been proposed including local generation of mitochondrial reactive oxygen species (mitoROS), a change in mitochondrial/cellular redox status, a fall in MgATP and an increase in lactate. Although each mechanism is based on compelling experimental evidence, they are all not without question. The current review aims to explore the importance of each of these signalling pathways in mediating the overall CB response to hypoxia. We suggest that there is unlikely to be a single mechanism, but instead multiple mitochondrial related signalling pathways are recruited at different PaO2s during hypoxia. Furthermore, it still remains to be determined if mitochondrial signalling acts independently or in partnership with extra-mitochondrial O2-sensors. |
| first_indexed | 2024-04-14T05:15:43Z |
| format | Article |
| id | doaj.art-c4720412d05e443a839c8745ac5c5775 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-14T05:15:43Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-c4720412d05e443a839c8745ac5c57752022-12-22T02:10:22ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2022-05-011310.3389/fphys.2022.908617908617Are Multiple Mitochondrial Related Signalling Pathways Involved in Carotid Body Oxygen Sensing?Andrew P. Holmes0Agnieszka Swiderska1Demitris Nathanael2Hayyaf S. Aldossary3Hayyaf S. Aldossary4Clare J. Ray5Andrew M. Coney6Prem Kumar7School of Biomedical Sciences, Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United KingdomUnit of Cardiac Physiology, Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomSchool of Biomedical Sciences, Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United KingdomSchool of Biomedical Sciences, Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United KingdomCollege of Medicine, Basic Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi ArabiaSchool of Biomedical Sciences, Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United KingdomSchool of Biomedical Sciences, Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United KingdomSchool of Biomedical Sciences, Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United KingdomIt is generally acknowledged that the carotid body (CB) type I cell mitochondria are unique, being inhibited by relatively small falls in PaO2 well above those known to inhibit electron transport in other cell types. This feature is suggested to allow for the CB to function as an acute O2 sensor, being stimulated and activating systemic protective reflexes before the metabolism of other cells becomes compromised. What is less clear is precisely how a fall in mitochondrial activity links to type I cell depolarisation, a process that is required for initiation of the chemotransduction cascade and post-synaptic action potential generation. Multiple mitochondrial/metabolic signalling mechanisms have been proposed including local generation of mitochondrial reactive oxygen species (mitoROS), a change in mitochondrial/cellular redox status, a fall in MgATP and an increase in lactate. Although each mechanism is based on compelling experimental evidence, they are all not without question. The current review aims to explore the importance of each of these signalling pathways in mediating the overall CB response to hypoxia. We suggest that there is unlikely to be a single mechanism, but instead multiple mitochondrial related signalling pathways are recruited at different PaO2s during hypoxia. Furthermore, it still remains to be determined if mitochondrial signalling acts independently or in partnership with extra-mitochondrial O2-sensors.https://www.frontiersin.org/articles/10.3389/fphys.2022.908617/fullcarotid bodyhypoxiamitochondriasuccinatearterial chemoreceptorO2 sensor |
| spellingShingle | Andrew P. Holmes Agnieszka Swiderska Demitris Nathanael Hayyaf S. Aldossary Hayyaf S. Aldossary Clare J. Ray Andrew M. Coney Prem Kumar Are Multiple Mitochondrial Related Signalling Pathways Involved in Carotid Body Oxygen Sensing? Frontiers in Physiology carotid body hypoxia mitochondria succinate arterial chemoreceptor O2 sensor |
| title | Are Multiple Mitochondrial Related Signalling Pathways Involved in Carotid Body Oxygen Sensing? |
| title_full | Are Multiple Mitochondrial Related Signalling Pathways Involved in Carotid Body Oxygen Sensing? |
| title_fullStr | Are Multiple Mitochondrial Related Signalling Pathways Involved in Carotid Body Oxygen Sensing? |
| title_full_unstemmed | Are Multiple Mitochondrial Related Signalling Pathways Involved in Carotid Body Oxygen Sensing? |
| title_short | Are Multiple Mitochondrial Related Signalling Pathways Involved in Carotid Body Oxygen Sensing? |
| title_sort | are multiple mitochondrial related signalling pathways involved in carotid body oxygen sensing |
| topic | carotid body hypoxia mitochondria succinate arterial chemoreceptor O2 sensor |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2022.908617/full |
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