Overloading of stable and exclusion of unstable human superoxide dismutase-1 variants in mitochondria of murine amyotrophic lateral sclerosis models.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Daniel BergemalmStefan L Marklund

Abstract

Mutants of human superoxide dismutase-1 (hSOD1) cause amyotrophic lateral sclerosis (ALS), and mitochondria are thought to be primary targets of the cytotoxic action. The high expression rates of hSOD1s in transgenic ALS models give high levels of the stable mutants G93A and D90A as well as the wild-type human enzyme, significant proportions of which lack Cu and the intrasubunit disulfide bond. The endogenous murine SOD1 (mSOD1) also lacks Cu and is disulfide reduced but is active and oxidized in mice expressing the low-level unstable mutants G85R and G127insTGGG. The possibility that the molecular alterations may cause artificial loading of the stable hSOD1s into mitochondria was explored. Approximately 10% of these hSOD1s were localized to mitochondria, reaching levels 100-fold higher than those of mSOD1 in control mice. There was no difference between brain and spinal cord and between stable mutants and the wild-type hSOD1. mSOD1 was increased fourfold in mitochondria from high-level hSOD1 mice but was normal in those with low levels, suggesting that the Cu deficiency and disulfide reduction cause mitochondrial overloading. The levels of G85R and G127insTGGG mutant hSOD1s in mitochondria were 100- and 1000-fold lower than th...Continue Reading

Citations

Jun 21, 2008·Neuromolecular Medicine·P Hemachandra Reddy
May 9, 2007·Nature Medicine·Rishi RakhitAvijit Chakrabartty
Feb 26, 2008·Proceedings of the National Academy of Sciences of the United States of America·Christine Vande VeldeDon W Cleveland
Nov 17, 2010·Proceedings of the National Academy of Sciences of the United States of America·Quan LiTimothy M Miller
Aug 20, 2011·The Journal of Biological Chemistry·Emily S StierenDarren Boehning
Mar 29, 2008·Antioxidants & Redox Signaling·Mauro CozzolinoMaria Teresa Carrì
Aug 16, 2008·Human Molecular Genetics·Hibiki Kawamata, Giovanni Manfredi
Feb 24, 2009·Human Molecular Genetics·Lijun WangRaymond P Roos
Aug 11, 2011·Human Molecular Genetics·Maria Grazia PesaresiMauro Cozzolino
Oct 3, 2012·Human Molecular Genetics·Karin S GraffmoThomas Brännström
Jan 1, 2009·Neurology International·Hisashi NaraiKoji Abe
Aug 24, 2007·Proceedings of the National Academy of Sciences of the United States of America·Per ZetterströmStefan L Marklund
Oct 19, 2012·Neuromolecular Medicine·Per ZetterströmStefan L Marklund
Apr 25, 2007·Scandinavian Journal of Clinical and Laboratory Investigation·J Iłzecka
Apr 5, 2012·Amyotrophic Lateral Sclerosis : Official Publication of the World Federation of Neurology Research Group on Motor Neuron Diseases·Sarah Pickles, Christine Vande Velde
Jan 27, 2016·Acta Neuropathologica Communications·Eiichi TokudaStefan L Marklund
Sep 24, 2015·Proceedings of the National Academy of Sciences of the United States of America·Jens DanielssonMikael Oliveberg
Sep 8, 2009·Experimental Neurology·Luc Dupuis
Nov 13, 2008·Journal of the Neurological Sciences·Stefania CortiGiacomo P Comi
Sep 27, 2008·Neurobiology of Disease·Toni AhtoniemiJari Koistinaho
Sep 16, 2008·Neurobiology of Disease·Alberto FerriMaria Teresa Carrì
Dec 3, 2014·Biochimica Et Biophysica Acta·Varda Shoshan-BarmatzShambhoo Sharan Tripathi
Jun 19, 2012·Molecular and Cellular Neurosciences·Mauro CozzolinoMaria Teresa Carrì
Aug 11, 2011·Progress in Neurobiology·Mauro Cozzolino, Maria Teresa Carrì
Aug 1, 2015·Translational Neurodegeneration·Zhen JiangXinglong Wang
Oct 4, 2006·Neuron·Séverine BoilléeDon W Cleveland
Nov 9, 2010·Biochemical and Biophysical Research Communications·Christine KlöppelJan Riemer
Aug 24, 2016·Proceedings of the National Academy of Sciences of the United States of America·Marcel F Leyton-JaimesAdrian Israelson
Aug 30, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ivana Sirangelo, Clara Iannuzzi
Feb 28, 2018·Journal of Neurochemistry·Ju GaoXinglong Wang
Aug 23, 2006·Nature Reviews. Neuroscience·Piera Pasinelli, Robert H Brown
Oct 16, 2009·Journal of Neurophysiology·Arnaud Pambo-PamboJean-Patrick Gueritaud

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