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dc.contributor.authorMorales Pérez, Ingrid 
dc.contributor.authorSánchez, Alberto
dc.contributor.authorPuertas Avendaño, Ricardo
dc.contributor.authorRodríguez Sabaté, Clara
dc.contributor.authorPérez Barreto, Adrián
dc.contributor.authorRodríguez, Manuel 
dc.contributor.otherCiencias Médicas Básicas
dc.contributor.otherGrupo de Neurobiología y Neurología Experimental
dc.date.accessioned2024-07-29T20:07:49Z
dc.date.available2024-07-29T20:07:49Z
dc.date.issued2020
dc.identifier.urihttp://riull.ull.es/xmlui/handle/915/38593
dc.description.abstractMitophagy is essential for the health of dopaminergic neurons because mitochondrial damage is a keystone of Parkinson's disease. The aim of the present work was to study the degradation of mitochondria in the degenerating dopaminergic synapse. Adult Sprague–Dawley rats and YFP-Mito-DAn mice with fluorescent mitochondria in dopaminergic neurons were injected in the lateral ventricles with 6-hydroxydopamine, a toxic that inhibits the mitochondrial chain of dopaminergic neurons and blockades the axonal transport. Dopaminergic terminals closest to the lateral ventricle showed an axonal fragmentation and an accumulation of damaged mitochondria in 2–9 μ saccular structures (spheroids). Damaged mitochondria accumulated in spheroids initiated (showing high Pink1, parkin, ubiquitin, p-S65-Ubi, AMBRA1, and BCL2L13 immunoreactivity and developing autophagosomes) but did not complete (mitochondria were not polyubiquitinated, autophagosomes had no STX17, and no lysosomes were found in spheroids) the mitophagy process. Then, spheroids were penetrated by astrocytic processes and DAergic mitochondria were transferred to astrocytes where they were polyubiquitinated (UbiK63+) and linked to mature autophagosomes (STX17+) which became autophagolysosomes (Lamp1/Lamp2 which co-localized with LC3). Present data provide evidence that the mitophagy of degenerating dopaminergic terminals starts in the dopaminergic spheroids and finishes in the surrounding astrocytes (spheroid-mediated transmitophagy). The neuron-astrocyte transmitophagy could be critical for preventing the release of damaged mitochondria to the extracellular medium and the neuro-inflammatory activity which characterizes Parkinson's disease.en
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.relation.ispartofseriesGLIA, 2020;68
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.titleNeuroglial transmitophagy and Parkinson's diseaseen
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1002/glia.23839
dc.subject.keywordastrocyteen
dc.subject.keyworddopaminergic neuronsen
dc.subject.keywordmitochondriaen
dc.subject.keywordParkinson's diseaseen
dc.subject.keywordtransmitophagyen


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