Artículos de revistas
Ryanodine receptor-mediated Ca2 release underlies iron-induced mitocondrial fission and stimulates mitocondrial Ca2 up take in primary hippocampal neurons
Fecha
2014Registro en:
Frontiers in Molecular Neuroscience, March2014 | Volume7 | Article 13 |
doi: 10.3389/fnmol.2014.00013
Autor
San Martín Rovirosa, Carol
Paula Lima, Andrea
García, Alejandra
Barattini, Pablo
Hartel, Steffen
Núñez González, Marco
Hidalgo Tapia, María Cecilia
Institución
Resumen
Mountingevidenceindicatesthatironaccumulationimpairsbrainfunction.Wehavereportedpreviouslythatadditionofsub-lethalconcentrationsofirontoprimaryhippocampalneuronsproducesCa2+signalsandpromotescytoplasmicgenerationofreactiveoxygenspecies.TheseCa2+signals,whichemergewithinsecondsafterironaddition,arisemostlyfromCa2+releasethroughtheredox-sensitiveryanodinereceptor(RyR)channelspresentintheendoplasmicreticulum.Wehavereportedalsothatadditionofsynaptotoxicamyloid-βoligomerstoprimaryhippocampalneuronsstimulatesRyR-mediatedCa2+release,generatinglong-lastingCa2+signalsthatactivateCa2+-sensitivecellulareffectorsandpromotethedisruptionofthemitochondrialnetwork.Here,wedescribethat24hincubationofprimaryhippocampalneuronswithironenhancedagonist-inducedRyR-mediatedCa2+releaseandpromotedmitochondrialnetworkfragmentationin43%ofneurons,aresponsesignificantlypreventedbyRyRinhibitionandbytheantioxidantagentN-acetyl-L-cysteine.StimulationofRyR-mediatedCa2+releasebyaRyRagonistpromotedmitochondrialCa2+uptakeincontrolneuronsandiniron-treatedneuronsthatdisplayednon-fragmentedmitochondria,butnotinneuronswithfragmentedmitochondria.Yet,theglobalcytoplasmicCa2+increaseinducedbytheCa2+ionophoreionomycinpromptedsignificantmitochondrialCa2+uptakeinneuronswithfragmentedmitochondria,indicatingthatfragmentationdidnotpreventmitochondrialCa2+uptakebutpresum-ablydecreasedthefunctionalcouplingbetweenRyR-mediatedCa2+releaseandthemitochondrialCa2+uniporter.Takentogether,ourresultsindicatethatstimulationofredox-sensitiveRyR-mediatedCa2+releasebyironcausessignificantneuronalmitochondrialfragmentation,whichpresumablycontributestotheimpairmentofneuronalfunctionproducedbyironaccumulation.