Mitochondrial permeability transition pore induces mitochondria injury in Huntington disease

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dc.contributor.authorQuintanilla, Rodrigo A.
dc.contributor.authorJin, Youngnam N.
dc.contributor.authorBernhardi Montgomery, Rommy von
dc.contributor.authorJohnson, Gail V.
dc.date.accessioned2019-10-17T15:02:12Z
dc.date.available2019-10-17T15:02:12Z
dc.date.issued2013
dc.date.updated2019-10-14T18:53:33Z
dc.description.abstractAbstract Background Mitochondrial impairment has been implicated in the pathogenesis of Huntington’s disease (HD). However, how mutant huntingtin impairs mitochondrial function and thus contributes to HD has not been fully elucidated. In this study, we used striatal cells expressing wild type (STHdhQ7/Q7) or mutant (STHdhQ111/Q111) huntingtin protein, and cortical neurons expressing the exon 1 of the huntingtin protein with physiological or pathological polyglutamine domains, to examine the interrelationship among specific mitochondrial functions. Results Depolarization induced by KCl resulted in similar changes in calcium levels without compromising mitochondrial function, both in wild type and mutant cells. However, treatment of mutant cells with thapsigargin (a SERCA antagonist that raises cytosolic calcium levels), resulted in a pronounced decrease in mitochondrial calcium uptake, increased production of reactive oxygen species (ROS), mitochondrial depolarization and fragmentation, and cell viability loss. The mitochondrial dysfunction in mutant cells was also observed in cortical neurons expressing exon 1 of the huntingtin protein with 104 Gln residues (Q104-GFP) when they were exposed to calcium stress. In addition, calcium overload induced opening of the mitochondrial permeability transition pore (mPTP) in mutant striatal cells. The mitochondrial impairment observed in mutant cells and cortical neurons expressing Q104-GFP was prevented by pre-treatment with cyclosporine A (CsA) but not by FK506 (an inhibitor of calcineurin), indicating a potential role for mPTP opening in the mitochondrial dysfunction induced by calcium stress in mutant huntingtin cells. Conclusions Expression of mutant huntingtin alters mitochondrial and cell viability through mPTP opening in striatal cells and cortical neurons.
dc.fuente.origenBiomed Central
dc.identifier.citationMolecular Neurodegeneration. 2013 Dec 11;8(1):45
dc.identifier.doi10.1186/1750-1326-8-45
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/26740
dc.identifier.urihttps://doi.org/10.1186/1750-1326-8-45
dc.identifier.wosidWOS:000328979600001
dc.issue.numeroNo. 45
dc.language.isoen
dc.nota.accesoContenido completo
dc.pagina.final19
dc.pagina.inicio1
dc.revistaMolecular Neurodegenerationes_ES
dc.rightsacceso abierto
dc.rights.holderQuintanilla et al.; licensee BioMed Central Ltd.
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.subject.otherEnfermedad de Huntingtones_ES
dc.subject.otherMitocondriases_ES
dc.subject.otherCerebro - Enfermedadeses_ES
dc.titleMitochondrial permeability transition pore induces mitochondria injury in Huntington diseasees_ES
dc.typeartículo
dc.volumenVol. 8
sipa.codpersvinculados1010409
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