Mitophagy in the Retinal Pigment Epithelium of Dry Age-Related Macular Degeneration Investigated in the NFE2L2/PGC-1α-/- Mouse Model
| العنوان: | Mitophagy in the Retinal Pigment Epithelium of Dry Age-Related Macular Degeneration Investigated in the NFE2L2/PGC-1α-/- Mouse Model |
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| المؤلفون: | Sridevi Gurubaran, Iswariyaraja, Viiri, Johanna, Koskela, Ali, Hyttinen, Juha M.T., Paterno, Jussi J., Kis, Gréta, Antal, Miklós, Urtti, Arto, Kauppinen, Anu, Felszeghy, Szabolcs, Kaarniranta, Kai |
| المصدر: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 21, Iss 6, p 1976 (2020) |
| بيانات النشر: | MDPI, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, mitochondrial damage, NF-E2-Related Factor 2, Ubiquitin-Protein Ligases, Retinal Pigment Epithelium, Article, age-related macular disease, lcsh:Chemistry, Macular Degeneration, Mice, Lysosomal-Associated Membrane Protein 2, oxidative stress, Animals, lcsh:QH301-705.5, Mitophagy, protein aggregates, autolysosomal fusion, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, eye diseases, Mitochondria, lcsh:Biology (General), lcsh:QD1-999, ageing, sense organs, Lysosomes, Microtubule-Associated Proteins, Protein Kinases, Gene Deletion |
| الوصف: | Increased oxidative stress and mitochondrial damage are observed in protein aggregation diseases, such as age-related macular degeneration (AMD). We have recently reported elevated levels of oxidative stress markers, damaged mitochondria, accumulating lysosomal lipofuscin and extracellular drusen-like structures in the retinal pigment epithelial cells (RPE) of the dry AMD-resembling NFE2L2/PGC1α double knockout (dKO) mouse model. Here, we provide evidence of a disturbance in the autolysosomal machinery handling mitochondrial clearance in the RPE cells of one-year-old NFE2L2/PGC1α-deficient mice. Confocal immunohistochemical analysis revealed an upregulation of autophagosome marker microtubule-associated proteins 1A/1B light chain 3B (LC3B) as well as numerous mitophagy markers, such as PTE-induced putative kinase 1 (PINK1) and E3 ubiquitin ligase (PARKIN) together with damaged mitochondria. However, we detected no evidence of increased autolysosome formation in transmission electron micrographs or of colocalization of lysosomal marker LAMP2 (lysosome-associated membrane protein 2) and the mitochondrial marker ATP synthase β in confocal micrographs. Interestingly, we observed an upregulation of late autolysosomal fusion Ras-related protein (Rab7) in the perinuclear space of RPE cells together with autofluorescence aggregates. Our results reveal that there is at least a relative decrease of mitophagy in the RPE cells of NFE2L2/PGC1α dKO mice. This further supports the hypothesis that mitophagy is a putative therapy target in AMD-like pathology. |
| اللغة: | English |
| تدمد: | 1422-0067 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::96ab333fbed33c9186ce6d587a27b783 http://europepmc.org/articles/PMC7139489 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.pmid.dedup....96ab333fbed33c9186ce6d587a27b783 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
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