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 O-2 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 P(a)O(2)s during hypoxia. Furthermore, it still remains to be determined if mitochondrial signalling acts independently or in partnership with extra-mitochondrial O-2-sensors.

Automated summary

It is widely recognized that the mitochondria in type I cells of the carotid body (CB) are unique, as they can be inhibited by relatively small decreases in PaO2 compared to other cell types. This characteristic allows the CB to function as an acute oxygen sensor, being stimulated and activating protective reflexes before other cells' metabolism is compromised. However, the exact mechanism of how a decrease in mitochondrial activity leads to depolarization of type I cells is still unclear. This review explores the significance of various signaling pathways in mediating the overall CB response to hypoxia, suggesting that multiple mitochondria-related signaling pathways are likely involved at different oxygen levels (P(a)O(2)s) during hypoxia. Additionally, it remains to be determined whether mitochondrial signaling acts independently or in collaboration with extramitochondrial oxygen sensors.