Redox signaling in acute oxygen sensing

Abstract

Acute oxygen (O2) sensing is essential for individuals to survive under hypoxic conditions. The carotid body (CB) is the main peripheral chemoreceptor, which contains excitable and O2-sensitive glomus cells with O2-regulated ion channels. Upon exposure to acute hypoxia, inhibition of K+ channels is the signal that triggers cell depolarization, transmitter release and activation of sensory fibers that stimulate the brainstem respiratory center to produce hyperventilation. The molecular mechanisms underlying O2 sensing by glomus cells have, however, remained elusive. Here we discuss recent data demonstrating that ablation of mitochondrial Ndufs2 gene selectively abolishes sensitivity of glomus cells to hypoxia, maintaining responsiveness to hypercapnia or hypoglycemia. These data suggest that reactive oxygen species and NADH generated in mitochondrial complex I during hypoxia are signaling molecules that modulate membrane K+ channels. We propose that the structural substrates for acute O2 sensing in CB glomus cells are “O2-sensing microdomains” formed by mitochondria and neighboring K+ channels in the plasma membrane.

Acute oxygen sensing by the carotid body: a rattlebag of molecular mechanisms

“…However, within the past two decades research from the laboratory of Dr Jose Lopez-Barneo has worked towards a comprehensive mechanism of acute oxygen sensing that critically relies on the production of reactive oxygen species by Type I cell mitochondria, and has focused specifically on complex I of the electron transport chain (Ortega-Saenz et al 2003). Recently these mechanisms were described in detail and indicated that hypoxic inhibition of mitochondrial electron transport resulted in increased production of reactive oxygen species and reduced pyridine nucleotides from complex I of the mitochondria (Fernandez-Aguera et al 2015;Gao et al 2017b). This increase in reactive oxygen species production was hypothesized to change the redox status of membrane ion channels and thus initiate excitation.…”

“…; Gao et al . ). This increase in reactive oxygen species production was hypothesized to change the redox status of membrane ion channels and thus initiate excitation.…”

“…; Gao et al . ) and when one considers the potential interactions between mitochondria and plasma membrane, the physical arrangement of cellular organelles may be critical for a cell to transduce a hypoxic signal. Indeed as can be seen in Fig.…”

“…Finally, the presentation touched on the unique subcellular microenvironment that exists in carotid body Type I cells. Others have stressed the importance of this microenvironment (Varas et al 2007;Gao et al 2017b) and when one considers the potential interactions between mitochondria and plasma membrane, the physical arrangement of cellular organelles may be critical for a cell to transduce a hypoxic signal. Indeed as can be seen in Fig.…”

Efectos inducidos por la hipoxia crónica intermitente en rata y cobaya como modelos animales de la apnea obstructiva del sueño

“…Hipótesis de señalización del complejo I mitocondrial. Recientemente se ha descrito que la inhibición hipóxica del transporte de electrones mitocondrial produce un aumento de ROS y nucleótidos de piridina reducidos del complejo I de las mitocondrias 70,71 . Este aumento en la producción de ROS cambiaría el estado redox de los canales iónicos de membrana y, por lo tanto, iniciaría la excitación.…”