RT Journal Article
T1 Acute O2 Sensing: Role of Coenzyme QH2/Q Ratio and Mitochondrial ROS Compartmentalization.
A1 Arias-Mayenco, Ignacio
A1 Gonzalez-Rodriguez, Patricia
A1 Torres-Torrelo, Hortensia
A1 Gao, Lin
A1 Fernandez-Agüera, M Carmen
A1 Bonilla-Henao, Victoria
A1 Ortega-Saenz, Patricia
A1 Lopez-Barneo, Jose
K1 NAD(+) regeneration
K1 acute oxygen sensing
K1 arterial chemoreceptors
K1 carotid body
K1 coenzyme QH(2)/Q ratio
K1 glomus cells
K1 inducible Ndufs2 knockout
K1 metabolic specifications
K1 mitochondrial ROS compartmentalization
K1 mitochondrial complex I signaling
AB Acute O2 sensing by peripheral chemoreceptors is essential for mammalian homeostasis. Carotid body glomus cells contain O2-sensitive ion channels, which trigger fast adaptive cardiorespiratory reflexes in response to hypoxia. O2-sensitive cells have unique metabolic characteristics that favor the hypoxic generation of mitochondrial complex I (MCI) signaling molecules, NADH and reactive oxygen species (ROS), which modulate membrane ion channels. We show that responsiveness to hypoxia progressively disappears after inducible deletion of the Ndufs2 gene, which encodes the 49 kDa subunit forming the coenzyme Q binding site in MCI, even in the presence of MCII substrates and chemical NAD+ regeneration. We also show contrasting effects of physiological hypoxia on mitochondrial ROS production (increased in the intermembrane space and decreased in the matrix) and a marked effect of succinate dehydrogenase activity on acute O2 sensing. Our results suggest that acute responsiveness to hypoxia depends on coenzyme QH2/Q ratio-controlled ROS production in MCI.
PB Cell Press
YR 2018
FD 2018-06-07
LK http://hdl.handle.net/10668/12571
UL http://hdl.handle.net/10668/12571
LA en
NO Arias-Mayenco I, González-Rodríguez P, Torres-Torrelo H, Gao L, Fernández-Agüera MC, Bonilla-Henao V, et al. Acute O2 Sensing: Role of Coenzyme QH2/Q Ratio and Mitochondrial ROS Compartmentalization. Cell Metab. 2018 Jul 3;28(1):145-158.e4.
NO This research was supported by the Botín Foundation, the Spanish Ministries of Science and Innovation and Health (SAF2012-39343, SAF2016-74990-R), and the European Research Council (ERC Advanced Grant PRJ201502629). H.T.-T. received a predoctoral fellowship (FPI program) from the Spanish Government. We thank Dr. Elizabeth Pintado (University of Seville, Spain) for comments and suggestions. We also thank IBiS staff for technical assistance. We are indebted to Dr. Navdeep S. Chandel (Northwestern University, USA) for bringing to our attention the use of α-ketobutyrate and to Drs. Richard C. Hartley (University of Glasgow, UK) and Michael P. Murphy (University of Cambridge, UK) for valuable suggestions on the use of MitoNeoD.
DS RISalud
RD Apr 19, 2025