Characterization of SCaMC-3, the mitochondrial ATP-Mg/Pi carrier present in liver and brain

• Autores: Ignacio Amigo De al Huerga
• Directores de la Tesis: Jorgina Satrústegui Gil-Delgado (dir. tes.), Araceli del Arco Martínez (dir. tes.)
• Lectura: En la Universidad Autónoma de Madrid ( España ) en 2013
• Idioma: inglés
• Tribunal Calificador de la Tesis: José Manuel Cuezva Marcos (presid.), Joaquín Jordán Bueso (secret.), Susana Cadenas Álvarez (voc.), Vicente Rubio Zamora (voc.), Christos Chinopoulos (voc.)
• Materias:
  • Ciencias de la vida
    • Biología molecular
• Enlaces
  • Tesis en acceso abierto en: Biblos-e Archivo
• Resumen

  • The ATP­Mg/Pi carrier has been described as a putative regulator of gluconeogenesis and the urea cycle, as well as being responsible for the uptake of nucleotides that takes place after birth in newborn liver mitochondria. In addition, recent work has implicated the carrier in mitochondrial calcium homoeostasis and as a regulator of susceptibility to calcium­overload stimuli. In the present work we have studied the function of SCaMC­3, the paralog of the mitochondrial ATP­Mg/Pi carrier found in brain and liver, through the characterization of a mouse model deficient for the protein. Our results indicate that absence of the protein increases the level of liver injury markers in blood and decreases the plasma concentration of urea. In addition, we show that SCaMC­3 can favour coupling between electron transport chain activity and oxidative phosphorylation in adenine nucleotide­depleted mitochondria, a situation similar to the one observed in newborn liver mitochondria, through a mechanism dependent on extramitochondrial calcium that does not require calcium entry in the mitochondria. We have also described that SCaMC­3 is a target of glucagon signalling, being responsible for the uptake of nucleotides by liver mitochondria and the stimulation of respiration observed after its administration. Finally, we show that lack of SCaMC­3 renders mice more susceptible to kainic acid­induced seizures and astrogliosis, but more resistant to ischemia/reperfusion injury both in vivo, with smaller infarct volume after middle cerebral arterial occlusion, and in vitro, with reduced cell death after oxygen and glucose deprivation.