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Testosterone increases apoptotic cell death and decreases mitophagy in Leber’s hereditary optic neuropathy cells

dc.abstract.enLeber’s hereditary optic neuropathy (LHON) is one of the most common mitochondrial diseases caused by point mutations in mitochondrial DNA (mtDNA). The majority of diagnosed LHON cases are caused by a point mutation at position 11,778 in the mitochondrial genome. LHON mainly affects young men in their 20s and 30s with usually poor visual prognosis. It remains unexplained why men are more likely to develop the disease and why only retinal ganglion cells are affected. In this study, a cell model was used for the first time to investigate the influence of testosterone on the cell death mechanism apoptosis and on an autophagy/mitophagy. Cells with m.11778G > A were found to be significantly more susceptible to nucleosome formation and effector caspase activation that serve as hallmarks of apoptotic cell death. Cells having this mutation expressed higher levels of mitophagic receptors BNIP3 and BNIP3L/Nix in a medium with testosterone. Moreover, cells having the mutation exhibited greater mitochondrial mass, which suggests these cells have a decreased cell survival. The observed decrease in cell survival was supported by the observed increase in apoptotic cell death. Autophagy was analyzed after inhibition with Bafilomycin A1 (Baf A1). The results indicate impairment in autophagy in LHON cells due to lower autophagic flux supported by observed lower levels of autophagosome marker LC3-II. The observed impaired lower autophagic flux in mutant cells correlated with increased levels of BNIP3 and BNIP3L/Nix in mutant cells.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorHajieva, Parvana
dc.contributor.authorKorwin, Magdalena
dc.contributor.authorOłdak, Monika
dc.contributor.authorJankauskaitė, Elona
dc.contributor.authorKodroń, Agata
dc.contributor.authorAmbroziak, Anna
dc.contributor.authorTońska, Katarzyna
dc.contributor.authorBartnik, Ewa
dc.date.accessioned2024-01-26T09:44:03Z
dc.date.available2024-01-26T09:44:03Z
dc.date.issued2020
dc.description.financePublikacja bezkosztowa
dc.description.number2
dc.description.volume61
dc.identifier.doi10.1007/S13353-020-00550-Y
dc.identifier.issn1234-1983
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/121742
dc.identifier.weblinkhttp://link.springer.com/content/pdf/10.1007/s13353-020-00550-y.pdf
dc.languageeng
dc.pbn.affiliationbiological sciences
dc.relation.ispartofJournal of Applied Genetics
dc.relation.pages195-203
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.titleTestosterone increases apoptotic cell death and decreases mitophagy in Leber’s hereditary optic neuropathy cells
dc.typeJournalArticle
dspace.entity.typePublication