{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:25:24Z","timestamp":1789050324440,"version":"build-2803163510"},"reference-count":78,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,3,13]],"date-time":"2020-03-13T00:00:00Z","timestamp":1584057600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","award":["722717"],"award-info":[{"award-number":["722717"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["296840"],"award-info":[{"award-number":["296840"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Kuopio University Hospital VTR grant","award":["5503743"],"award-info":[{"award-number":["5503743"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\/PGC1\u03b1 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\/PGC1\u03b1-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 \u03b2 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\/PGC1\u03b1 dKO mice. This further supports the hypothesis that mitophagy is a putative therapy target in AMD-like pathology.<\/jats:p>","DOI":"10.3390\/ijms21061976","type":"journal-article","created":{"date-parts":[[2020,3,18]],"date-time":"2020-03-18T08:20:44Z","timestamp":1584519644000},"page":"1976","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Mitophagy in the Retinal Pigment Epithelium of Dry Age-Related Macular Degeneration Investigated in the NFE2L2\/PGC-1\u03b1-\/- Mouse Model"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1863-9550","authenticated-orcid":false,"given":"Iswariyaraja","family":"Sridevi Gurubaran","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Viiri","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Koskela","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha M.T.","family":"Hyttinen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5442-4314","authenticated-orcid":false,"given":"Jussi J.","family":"Paterno","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gr\u00e9ta","family":"Kis","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Anatomy, Histology and Embryology, University of Debrecen, Medical and Health Science Centre, Nagyerdei krt. 98, H-4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2457-7387","authenticated-orcid":false,"given":"Mikl\u00f3s","family":"Antal","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Anatomy, Histology and Embryology, University of Debrecen, Medical and Health Science Centre, Nagyerdei krt. 98, H-4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arto","family":"Urtti","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, School of Pharmacy, University of Eastern Finland, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8254-0200","authenticated-orcid":false,"given":"Anu","family":"Kauppinen","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, School of Pharmacy, University of Eastern Finland, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szabolcs","family":"Felszeghy","sequence":"additional","affiliation":[{"name":"Institute of Dentistry and Biomedicine, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Kaarniranta","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Kuopio University Hospital, University of Eastern Finland, 70029 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1001\/archopht.119.10.1455","article-title":"Risk factors for age-related maculopathy: The Visual Impairment Project","volume":"119","author":"McCarty","year":"2001","journal-title":"Arch. 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