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

Journal of Applied Genetics
Elona JankauskaitėAgata Kodroń

Abstract

Leber'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 A...Continue Reading

References

Apr 4, 2000·Cell Death and Differentiation·R J Carmody, T G Cotter
Aug 21, 2001·Journal of the American Academy of Dermatology·L R Nelson, S E Bulun
Feb 21, 2002·Human Molecular Genetics·Alice WongGino A Cortopassi
Jan 9, 2003·American Journal of Human Genetics·P Yu-Wai-ManP F Chinnery
Nov 19, 2004·Journal of Neurology, Neurosurgery, and Psychiatry·C BattistiA Federico
Jun 29, 2006·The Journal of Biological Chemistry·Manuel EstradaBarbara E Ehrlich
Apr 5, 2007·European Journal of Human Genetics : EJHG·Anu PuomilaEeva Nikoskelainen
May 1, 2007·Experimental Eye Research·C CascioP Guarneri
Mar 18, 2008·IUBMB Life·Anna-Maria G Psarra, Constantine E Sekeris
Nov 28, 2008·The Journal of Biological Chemistry·Lina DuRobert S B Clark
Mar 4, 2009·Investigative Ophthalmology & Visual Science·Matthew Anthony KirkmanPatrick Yu-Wai-Man
Oct 15, 2010·Brain : a Journal of Neurology·Carla GiordanoValerio Carelli
Jul 3, 2013·Nature Cell Biology·Patricia BoyaPatrice Codogno
Mar 8, 2014·Journal of Molecular Endocrinology·Gabriela Capllonch-AmerMagdalena Gianotti
Mar 11, 2015·Biochimica Et Biophysica Acta·Paul A Ney
Aug 2, 2016·Mitochondrion·Nuri GuevenJamuna Chhetri
Nov 17, 2016·Mitochondrion·Elona JankauskaitėAgata Kodroń
May 4, 2017·The EMBO Journal·Lorena Esteban-MartínezPatricia Boya
Jan 28, 2018·Nature Communications·Silvia Márquez-JuradoFrancisco J Iborra
Jul 17, 2018·Endocrine Reviews·David J HandelsmanStephane Bermon

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Citations

Mar 17, 2021·Investigative Ophthalmology & Visual Science·Jessica M SkeieMark A Greiner
Jun 26, 2021·Human Molecular Genetics·Tiago M Bernardino GomesAmy E Vincent

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Methods Mentioned

BETA
Blood
Protein Assay
Fluorescence

Software Mentioned

ImageJ

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