The background of mitochondrial DNA haplogroup J increases the sensitivity of Leber's hereditary optic neuropathy cells to 2,5-hexanedione toxicity.

PloS One
Anna GhelliValerio Carelli

Abstract

Leber's hereditary optic neuropathy (LHON) is a maternally inherited blinding disease due to mitochondrial DNA (mtDNA) point mutations in complex I subunit genes, whose incomplete penetrance has been attributed to both genetic and environmental factors. Indeed, the mtDNA background defined as haplogroup J is known to increase the penetrance of the 11778/ND4 and 14484/ND6 mutations. Recently it was also documented that the professional exposure to n-hexane might act as an exogenous trigger for LHON. Therefore, we here investigate the effect of the n-hexane neurotoxic metabolite 2,5-hexanedione (2,5-HD) on cell viability and mitochondrial function of different cell models (cybrids and fibroblasts) carrying the LHON mutations on different mtDNA haplogroups. The viability of control and LHON cybrids and fibroblasts, whose mtDNAs were completely sequenced, was assessed using the MTT assay. Mitochondrial ATP synthesis rate driven by complex I substrates was determined with the luciferine/luciferase method. Incubation with 2,5-HD caused the maximal loss of viability in control and LHON cells. The toxic effect of this compound was similar in control cells irrespective of the mtDNA background. On the contrary, sensitivity to 2,5-HD indu...Continue Reading

References

Dec 15, 1978·Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie. Albrecht Von Graefe's Archive for Clinical and Experimental Ophthalmology·C RaittaM S Huuskonen
Oct 1, 1978·Environmental Health Perspectives·P S Spencer, H H Schaumburg
Jan 1, 1982·International Archives of Occupational and Environmental Health·L PerbelliniM S Venturini
Nov 1, 1993·Archives of Ophthalmology·M E CullomD R Johns
Jan 1, 1993·International Archives of Occupational and Environmental Health·Y TakeuchiM Iwata
May 1, 1996·Southern Medical Journal·R Meadows, A Verghese
Jan 1, 1996·Somatic Cell and Molecular Genetics·I Trounce, D C Wallace
May 20, 1996·Biochimica Et Biophysica Acta·M CantonG F Azzone
Nov 3, 1998·Brain : a Journal of Neurology·P MaruffJ Currie
Apr 27, 1999·The British Journal of Ophthalmology·K TsaoD R Johns
Dec 2, 2000·Nature Neuroscience·R BetarbetJ T Greenamyre
Dec 22, 2000·American Journal of Ophthalmology·J B KerrisonN J Newman
Feb 19, 2002·Neurochemistry International·Valerio CarelliAlfredo A Sadun
Mar 19, 2002·Journal of Medical Genetics·P Yu-Wai-ManP F Chinnery
Jun 11, 2002·Methods : a Companion to Methods in Enzymology·Giovanni ManfrediMarina Mattiazzi
Oct 3, 2002·Nature Medicine·Laura Bonetta
Mar 6, 2003·American Journal of Human Genetics·Joelle M van der WaltJeffery M Vance
Apr 25, 2003·Trends in Genetics : TIG·Valerio CarelliGiulia d'Amati
Jul 31, 2003·American Journal of Ophthalmology·Alfredo A SadunRubens Belfort
Aug 6, 2003·Neurotoxicology·Fabriziomaria Gobba, Alessandro Cavalleri
Aug 19, 2003·Nature Genetics·Pierre L RoubertouxCharles Cohen-Salmon
Feb 10, 2004·Progress in Retinal and Eye Research·Valerio CarelliAlfredo A Sadun
Apr 1, 2004·Molecular Cell·Rebeca Acín-PérezJosé A Enríquez
Feb 25, 2005·Brain : a Journal of Neurology·Steven R DanielsonGino A Cortopassi
Apr 14, 2005·European Journal of Human Genetics : EJHG·Daniele GhezziMassimo Zeviani
Nov 23, 2005·The Journal of Biological Chemistry·Durga Prasad MishraChandrima Shaha
Dec 29, 2005·American Journal of Human Genetics·Gavin HudsonPatrick F Chinnery
Oct 19, 2006·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Catherine McDermottJames J A Heffron
Jan 6, 2007·Journal of Neuro-ophthalmology : the Official Journal of the North American Neuro-Ophthalmology Society·Ruben N SanchezJohn L Keltner
Jun 6, 2007·Documenta Ophthalmologica. Advances in Ophthalmology·Atsushi MizotaEmiko Adachi-Usami
Feb 1, 2008·Investigative Ophthalmology & Visual Science·Anna GhelliMichela Rugolo
Mar 26, 2008·Ophthalmic Genetics·Suma P ShankarEdwin M Stone
Jun 19, 2008·Genetics·Douglas C Wallace

❮ Previous
Next ❯

Citations

Jul 5, 2011·Journal of Neurology·Elena Sánchez-FerreroVictoria Alvarez
Oct 15, 2010·Brain : a Journal of Neurology·Carla GiordanoValerio Carelli
Oct 27, 2010·PloS One·Giuseppina RoseUNKNOWN GEnetics of Healthy Ageing Project Consortium
Jan 22, 2011·Journal of Ophthalmology·Rajeshwari D Koilkonda, John Guy
Nov 17, 2012·Nature Reviews. Genetics·Eric A SchonMichio Hirano
Feb 26, 2015·Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis·Haixin YangChuan-Chao Wang
Dec 15, 2015·Brain : a Journal of Neurology·Valerio CarelliAlfredo A Sadun
Dec 2, 2015·Human Genetics·Mariangela SantorsolaMarcella Attimonelli
Feb 20, 2013·Mitochondrion·Periyasamy GovindarajKumarasamy Thangaraj
Nov 17, 2011·Biochimica Et Biophysica Acta·Valentina GiorgioPaolo Bernardi
Mar 9, 2012·Mitochondrial DNA·Ludmila Grzybowska-Szatkowska, Brygida Slaska
Feb 16, 2012·Epigenomics·Dina BellizziGiuseppe Passarino
Mar 16, 2018·Journal of the Peripheral Nervous System : JPNS·Raquel Guimarães-CostaJean-Marc Léger
May 8, 2018·Genes·Giulia LeoneLuisa Iommarini
Apr 30, 2020·International Journal of Molecular Sciences·Lei ZhouPascal Reynier
Feb 1, 2011·Seminars in Ophthalmology·Kurt Spiteri Cornish, Christopher Barras
Feb 6, 2020·Human Molecular Genetics·Nicolás Gutiérrez CortésChristophe Rocher
Dec 8, 2020·Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis·Zhaochang JiangYu Ding
Feb 25, 2021·Nature Reviews. Neurology·William L MackenRobert D S Pitceathly
Apr 4, 2021·Biomolecules·Alessandra Maresca, Valerio Carelli
Sep 7, 2021·Frontiers in Genetics·Samantha W JonesAna Alfirevic
Jul 19, 2017·Mitochondrion·Leonardo CaporaliValerio Carelli

❮ Previous
Next ❯

Datasets Mentioned

BETA
GQ304740

Methods Mentioned

BETA
PCR
Assay

Related Concepts

Related Feeds

Epidemiology of Aging

This feed focuses on epidemiology of aging and aging-related conditions, including Alzheimer’s disease, dementia, and age-associated cognitive impairment. Here is the latest research.

Related Papers

Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie
Jan Willem R Pott, Kwok H Wong
© 2022 Meta ULC. All rights reserved