RT info:eu-repo/semantics/article
T1 Neuroglial transmitophagy and Parkinson's disease
A1 Morales Pérez, Ingrid
A1 Sánchez, Alberto
A1 Puertas Avendaño, Ricardo
A1 Rodríguez Sabaté, Clara
A1 Pérez Barreto, Adrián
A1 Rodríguez, Manuel
A2 Ciencias Médicas Básicas
A2 Grupo de Neurobiología y Neurología Experimental
K1 astrocyte
K1 dopaminergic neurons
K1 mitochondria
K1 Parkinson's disease
K1 transmitophagy
AB Mitophagy is essential for the health of dopaminergic neurons because mitochondrialdamage is a keystone of Parkinson's disease. The aim of the present work was to studythe degradation of mitochondria in the degenerating dopaminergic synapse. AdultSprague–Dawley rats and YFP-Mito-DAn mice with fluorescent mitochondria in dopaminergic neurons were injected in the lateral ventricles with 6-hydroxydopamine, atoxic that inhibits the mitochondrial chain of dopaminergic neurons and blockades theaxonal transport. Dopaminergic terminals closest to the lateral ventricle showed anaxonal fragmentation and an accumulation of damaged mitochondria in 2–9 μ saccularstructures (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 notpolyubiquitinated, autophagosomes had no STX17, and no lysosomes were found inspheroids) the mitophagy process. Then, spheroids were penetrated by astrocytic processes and DAergic mitochondria were transferred to astrocytes where they werepolyubiquitinated (UbiK63+) and linked to mature autophagosomes (STX17+) whichbecame autophagolysosomes (Lamp1/Lamp2 which co-localized with LC3). Presentdata provide evidence that the mitophagy of degenerating dopaminergic terminalsstarts in the dopaminergic spheroids and finishes in the surrounding astrocytes (spheroid-mediated transmitophagy). The neuron-astrocyte transmitophagy could be criticalfor preventing the release of damaged mitochondria to the extracellular medium andthe neuro-inflammatory activity which characterizes Parkinson's disease.
YR 2020
FD 2020
LK http://riull.ull.es/xmlui/handle/915/38593
UL http://riull.ull.es/xmlui/handle/915/38593
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 12-nov-2024