Page 123 - CIBERER-2015-eng

Most relevant scientific articles
Research Groups
rueda cB, traBa J, amigo i, llorente-Folch i, gonZáleZ- sáncheZ P, Pardo B, esteBan Ja, del arco a, satrústeg- ui J. Mitochondrial ATP-Mg/Pi carrier SCaMC-3/Slc25a23 counteracts PARP-1-dependent fall in mitochondrial ATP caused by excitotoxic insults in neurons. J Neurosci. 2015 35(8):3566-81.
llorente-Folch i, rueda cB, Pardo B, sZaBadKai g, duchen mr, satrustegui J. The regulation of neuronal mitochondrial metabolism by calcium. J Physiol. 2015; 593(16):3447-62.
du J, rountree a, cleghorn Wm, contreras l, lindsaY KJ, sadileK m, gu h, dJuKoVic d, raFterY d, satrustegui J, KanoW m, chan l, tsang sh, sWeet ir, hurleY JB. Pho- totransduction influences metabolic flux and nucleotide metabolism in mouse retina. J Biol Chem. 2015 pii: jbc. M115.698985.
Highlights
We have advanced in the knowledge of the role of Ca2+-dependent mitochondrial metabolite carriers and the calcium uniporter complex in mitochondrial Ca2+ signalling and regulation of respiration in neu- rons (Llorente-Folch et al., JPhysiol).
We have determined the consequences of the de- ficiency of the ATP-Mg/Pi transporter SCaMC-3/Sl- c25a23 in neurons, by both in vitro and in vivo models of glutamate excitotoxicity. The transport of adenine nucleotides in mitochondria through SCaMC-3 was found to be essential to counteract the drop in mi- tochondrial ATP levels caused by PARP1 activation, an early event in glutamate excitotoxicity (Rueda et al., JNeurosci).
In collaboration with JB. Hurley (Univ. Washington) we have continued studying the function of Aralar/ AGC1 in the metabolism of the retina. It was found that light slows metabolic flow through glycolysis and the TCA cycle due to opposing effects mediated by Ca2+ on metabolic fate of α-KG, oxidation vs ex- port, findings revealed using Aralar/AGC1 KO mice (Du et al., JBC).
cascón a, comino-méndeZ i, currás-Freixes m, de cu- Bas aa, contreras l, richter s, PeitZsch m, manciKoVa V, inglada-PéreZ l, PéreZ-Barrios a, calataYud m, aZri- el s, Villar-Vicente r, aller J, setién F, moran s, garcía JF, río-machín a, letón r, gómeZ-graña á, aPellániZ- ruiZ m, roncador g, esteller m, rodrígueZ-antona c, satrústegui J, eisenhoFer g, urioste m, roBledo m. Whole-exome sequencing identifies MDH2 as a new familial paraganglioma gene. J Natl Cancer Inst. 2015; 107(5). pii: djv053.
garcía-BermúdeZ J, sáncheZ-aragó m, soldeVilla B, del arco a, nueVo-taPioles c, cueZVa Jm. PKA Phospho- rylates the ATPase Inhibitory Factor 1 and Inactivates Its Capacity to Bind and Inhibit the Mitochondrial H(+)-ATP Synthase. Cell Rep. 2015; 12(12):2143-55.
We have collaborated with CIBERER U713 (JMCuez- va) and U706 (AGascón) units in the functional anal- ysis of mitochondrial proteins involved in tumor de- velopment and OXPHOS regulation. In the first case, the analysis of PKA-mediated phosphorylation of the ATP synthase inhibitor IF1 revealed a role of IF1 phosphorylation status in regulating aerobic glyco- lysis and OXPHOs. (García-Bermúdez et al., CellRe- ports). In the second case, mutations in MDH2 have been identified as cause of familial paragangliomas, revealing the existence of a novel tumor susceptibil- ity gene (Cascón et al., JNatlCancerInst.).
We have established a protocol to detect “PTP- prone” mitochondria in MEFS and fibroblasts as a way to detect the possible involvement of the PTP in Rare and common diseases. At present, treatments against myopathies involving the PTP are being de- veloped and the protocols prepared may be used to evaluate these treatments in ER patients’ fibroblasts (ACCI2014 Project in collaboration with CIBERER units U729 U723).
Institution: Universidad Autónoma de Madrid · Contact: Centro de Biología Molecular Severo Ochoa Nicolás Cabrera, 1. Campus de Cantoblanco UAM. 28049 Madrid · Tel.: 91 196 46 21 / Fax 91 196 44 20 E.mail: [email protected]
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