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Mitochondrial Complex I Dysfunction and Peripheral Chemoreflex Sensitivity in a FASTK-Deficient Mice Model

  • Angela Gomez-NiñoEmail author
  • Inmaculada Docio
  • Jesus Prieto-Lloret
  • Maria Simarro
  • Miguel A. de la Fuente
  • Asuncion Rocher
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1071)

Abstract

The molecular mechanisms underlying O2-sensing by carotid body (CB) chemoreceptors remain undetermined. Mitochondria have been implicated, due to the sensitivity of CB response to electron transport chain (ETC) blockers. ETC is one of the major sources of reactive oxygen species, proposed as mediators in oxygen sensing. Fas-activated serine/threonine phosphoprotein is a sensor of mitochondrial stress that modulates protein translation to promote survival of cells exposed to adverse conditions. A translational variant of Fas-activated serine/threonine kinase (FASTK) is required for the biogenesis of ND6 mRNA, the mitochondrial encoded subunit 6 of the NADH dehydrogenase complex (Complex I). Ablating FASTK expression reduced Complex I activity in vivo by about 50%. We have tested the hypothesis of Complex I participation in O2-sensing structures by studying the effect of hypoxia in FASTK−/− knockout mice. Ventilatory response to acute hypoxia and hypercapnia tests showed similar sensitivity and CB catecholaminergic activity in knockout and wild type mice; hypoxic pulmonary vasoconstriction response also was similar. Pulmonary artery contractility in vitro, using small vessel myography, showed a significantly decreased relaxation to rotenone in knockout mice pre-constricted vessels with PGF. In conclusion, FASTK−/− knockout mice maintain respiratory chemoreflex under hypoxia and hypercapnia stress suggesting that completely functional Complex I ND6 protein is not required for these responses.

Keywords

Mitochondria Complex I. FASTK family proteins Carotid body chemoreceptors 

Notes

Acknowledgements

This work was supported by Grants BFU2015-63706R (MINECO, FEDER-UE) and CIBER CB06/06/0050 from ISCiii (Spain). The Authors thank R. Cantalapiedra and R. Carretero for technical assistance.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Angela Gomez-Niño
    • 1
    • 2
    Email author
  • Inmaculada Docio
    • 3
    • 2
  • Jesus Prieto-Lloret
    • 3
    • 2
  • Maria Simarro
    • 4
  • Miguel A. de la Fuente
    • 1
  • Asuncion Rocher
    • 3
    • 2
  1. 1.Departamento de Biologia Celular, Histologia y Farmacologia/IBGMUniversidad de Valladolid-CSICValladolidSpain
  2. 2.CIBER de Enfermedades Respiratorias (CIBERES)Instituto de Salud Carlos IIIMadridSpain
  3. 3.Departamento de Bioquimica, Biologia Molecular y Fisiologia/IBGMUniversidad de Valladolid-CSICValladolidSpain
  4. 4.Departamento de Enfermeria/IBGMUniversidad de ValladolidValladolidSpain

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