The role of mitophagy in neurogenesis and neurodegeneration
The vertebrate neural retina is a structure made up of six neuronal and one glial cell type, which arise from a pool of multipotent progenitor cells. We have previously shown that mitophagy is necessary for retinal development, since animals deficient in the protein that regulates mitophagy, NIX, sh...
| Autor: | |
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| Tipo de recurso: | tesis doctoral |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universidad Complutense de Madrid (UCM) |
| Repositorio: | Docta Complutense |
| Idioma: | inglés |
| OAI Identifier: | oai:docta.ucm.es:20.500.14352/4253 |
| Acceso en línea: | https://hdl.handle.net/20.500.14352/4253 |
| Access Level: | acceso abierto |
| Palabra clave: | 576.311.347(043.2) Mitochondria Mitocondrias Biología celular (Biología) 2407 Biología Celular |
| Sumario: | The vertebrate neural retina is a structure made up of six neuronal and one glial cell type, which arise from a pool of multipotent progenitor cells. We have previously shown that mitophagy is necessary for retinal development, since animals deficient in the protein that regulates mitophagy, NIX, show reduced numbers of retinal ganglion cells (RGC) in both the embryonic and adult retinas. In this doctoral thesis we want to further study the role of autophagy and mitophagy during retinal development, understand mitophagy levels at different stages of retinal development using MitoQC mitophagy reporter mice. The MitoQC reporter contains a tandem fusion protein (mCherryGFP) that targets the outer mitochondrial membrane (OMM). Under normal conditions, all mitochondria fluoresce in both green and red. During mitophagy, when mitochondria are transported to the lysosome, the GFP fluorescence is quenched by the acidic pH of the lysosome resulting in mitochondria marked red. Our data show that in the retina, many cell types show red dots indicative of mitophagy during different stages of embryonic development. In addition, we also show that we can induce mitophagy at different ages using pharmacological tools. Parkinson's disease (PD) is the second most prevalent neurological disease after Alzheimer's. The aetiology of Parkinson's disease is complex and unknown, although mitochondrial and lysosomal alterations play an important role. Mitophagy is impaired in patients and models with Parkinson's disease. PINK1 and Parkin are two proteins mutated in some PD patients that have a role in the control of mitophagy. Our data using the MitoQC animals injected with 6-OHDA show how mitophagy is decreased in dopaminergic neurons while the astrocytes present high levels of mitophagy. |
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