Mitochondrial permeability transition pore induces mitochondria injury in Huntington disease

Molecular Neurodegeneration
Rodrigo A QuintanillaGail V W Johnson

Abstract

Mitochondrial impairment has been implicated in the pathogenesis of Huntington's disease (HD). However, how mutant huntingtin impairs mitochondrial function and thus contributes to HD has not been fully elucidated. In this study, we used striatal cells expressing wild type (STHdhQ7/Q7) or mutant (STHdhQ111/Q111) huntingtin protein, and cortical neurons expressing the exon 1 of the huntingtin protein with physiological or pathological polyglutamine domains, to examine the interrelationship among specific mitochondrial functions. Depolarization induced by KCl resulted in similar changes in calcium levels without compromising mitochondrial function, both in wild type and mutant cells. However, treatment of mutant cells with thapsigargin (a SERCA antagonist that raises cytosolic calcium levels), resulted in a pronounced decrease in mitochondrial calcium uptake, increased production of reactive oxygen species (ROS), mitochondrial depolarization and fragmentation, and cell viability loss. The mitochondrial dysfunction in mutant cells was also observed in cortical neurons expressing exon 1 of the huntingtin protein with 104 Gln residues (Q104-GFP) when they were exposed to calcium stress. In addition, calcium overload induced opening ...Continue Reading

References

Mar 1, 1996·Annals of Neurology·M GuA H Schapira
Nov 25, 2000·Human Molecular Genetics·F TrettelM E MacDonald
Feb 22, 2001·Trends in Neurosciences·E CattaneoS Sipione
Apr 30, 2002·Trends in Cell Biology·Janet M Shaw, Jodi Nunnari
Jun 29, 2002·Nature Neuroscience·Alexander V PanovJ Timothy Greenamyre
Aug 2, 2003·Current Opinion in Cell Biology·Sidney V ScottJodi Nunnari
Oct 17, 2003·The Journal of Physiology·Julio F Turrens
Jul 1, 2004·Annals of Medicine·Leonardo Petrucelli, Ted M Dawson
Sep 10, 2004·American Journal of Physiology. Cell Physiology·Paul S BrookesShey-Shing Sheu
Mar 29, 2005·The Journal of Biological Chemistry·Emy BassoPaolo Bernardi
Apr 22, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Frédéric DariosMerle Ruberg
Jun 29, 2005·The Journal of Biological Chemistry·Tamara Milakovic, Gail V W Johnson
Nov 12, 2005·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·A G ValeraJ J Lucas
Nov 17, 2005·Nature Reviews. Neuroscience·Elena CattaneoMarzia Tartari
Feb 14, 2006·Neurobiology of Disease·Diane T W ChangIan J Reynolds
Oct 27, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jorge M A OliveiraA Cristina Rego
Feb 3, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Andrey Y AbramovMichael R Duchen
Feb 13, 2007·Apoptosis : an International Journal on Programmed Cell Death·Andrea Rasola, Paolo Bernardi
Mar 23, 2007·Nature Reviews. Molecular Cell Biology·Stefan J Riedl, Guy S Salvesen
Apr 28, 2007·Proceedings of the National Academy of Sciences of the United States of America·Michael ForteDennis Bourdette
Dec 14, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Herman B FernandesLynn A Raymond
Nov 29, 2008·Human Molecular Genetics·Hongmin WangMervyn J Monteiro
Dec 17, 2008·Annals of the New York Academy of Sciences·Andrew B Knott, Ella Bossy-Wetzel
Jan 10, 2009·Neurobiology of Disease·A Jennifer MortonJames M Wight
May 26, 2009·Neurobiology of Disease·Liliana MenalledDaniela Brunner
Jul 23, 2009·Brain Research Bulletin·Rodrigo A Quintanilla, Gail V W Johnson
Jul 28, 2010·Human Molecular Genetics·Jinho KimRobert J Ferrante
Dec 1, 2010·EMBO Molecular Medicine·Jorge M A Oliveira, Robert N Lightowlers

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Citations

Jul 30, 2014·Toxicology Letters·Patricia Santofimia-CastañoAntonio Gonzalez
Dec 3, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Isabel DenzerKristina Friedland
May 28, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Rosella Abeti, Andrey Y Abramov
Apr 16, 2016·Molecular Neurodegeneration·Evgeny D NekrasovSergey L Kiselev
Sep 14, 2014·Journal of Bioenergetics and Biomembranes·Juan Carlos Corona, Michael R Duchen
Aug 4, 2016·Biochemical and Biophysical Research Communications·Luana NaiaA Cristina Rego
Aug 25, 2016·Biochemical and Biophysical Research Communications·Magdalena CzeredysJacek Kuznicki
Sep 17, 2016·Mechanisms of Ageing and Development·Aris A Polyzos, Cynthia T McMurray
Sep 19, 2016·Biochemical and Biophysical Research Communications·Géraldine LiotEmmanuel Brouillet
Mar 7, 2018·Human Molecular Genetics·Silvia CorrochanoAbraham Acevedo-Arozena
Apr 6, 2018·Molecular Neurobiology·Juan A GodoyNibaldo C Inestrosa
Apr 18, 2018·Journal of Alzheimer's Disease : JAD·Juan M ZolezziNibaldo C Inestrosa
Jun 12, 2018·Aging Cell·Mathieu PanelDidier Morin
Jul 3, 2018·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yui YamazakiShogo Tokuyama
May 11, 2016·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Jia BakYun-Sik Choi
Feb 9, 2017·Oxidative Medicine and Cellular Longevity·Thirunavukkarasu VelusamyMahesh Kandasamy
Oct 24, 2017·Frontiers in Neuroscience·María J PérezRodrigo A Quintanilla
Aug 9, 2016·Journal of Bioenergetics and Biomembranes·Stephen HurstShey-Shing Sheu
Oct 23, 2014·The Journal of Biological Chemistry·Juan A GodoyNibaldo C Inestrosa
Nov 9, 2019·Scientific Reports·Rodrigo F M de AlmeidaRadosław Starosta
Jan 5, 2021·Frontiers in Cell and Developmental Biology·Hyunsu JungSeok-Kyu Kwon
Feb 2, 2020·Medical Hypotheses·Annette Offringa-Hup
May 1, 2021·International Journal of Molecular Sciences·Laurent SchwartzMiroslav Radman
Jul 24, 2021·Frontiers in Molecular Biosciences·Thomas PaßDavid Pla-Martín
Jul 17, 2021·Life Sciences·KyoungJoo Cho, Gyung Whan Kim
May 30, 2021·The Journal of Pharmacy and Pharmacology·Sudhanshu SharmaPravir Kumar

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Methods Mentioned

BETA
transgenic
confocal microscopy
PCR
transfection

Software Mentioned

Image
Image Pro
LCS Leica confocal
Pro Plus

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