Ketogenic treatment reduces deleted mitochondrial DNAs in cultured human cells

Annals of Neurology
Sumana SantraEric A Schon

Abstract

Impairment of mitochondrial energy metabolism has been associated with a wide range of human disorders. Large-scale partial deletions of mitochondrial DNA (mtDNA) cause sporadic Kearns-Sayre syndrome, a fatal multisystem disorder, in which the majority of mtDNAs in affected tissues have deletions (Delta-mtDNAs). Since most mtDNA-related diseases, including Kearns-Sayre syndrome, are recessive, only a few wild-type mtDNAs can compensate for the deleterious effects of many Delta-mtDNAs. We have developed a pharmacological approach to reduce the proportion of Delta-mtDNAs in vitro, in which we grow cells in medium containing ketone bodies, replacing glucose as the carbon source. Cells containing 100% Delta-mtDNA died after 5 days of treatment, whereas those containing 100% wild-type mtDNA survived. Furthermore, in a cloned heteroplasmic cell line, the proportion of wild-type mtDNA increased from 13% initially to approximately 22% after 5 days in ketogenic medium and was accompanied by a dramatic improvement in mitochondrial protein synthesis. We also present evidence that treatment with ketone bodies caused "heteroplasmic shifting" not only among cells (ie, intercellular selection) but also within cells (ie, intracellular selectio...Continue Reading

References

Oct 1, 1992·Biochemical Medicine and Metabolic Biology·B H RobinsonD C Wallace
Sep 1, 1991·Experimental Cell Research·M Satoh, T Kuroiwa
Dec 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·J HayashiI Nonaka
May 18, 1989·The New England Journal of Medicine·C T MoraesS Servidei
Sep 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·K W Lanks
Apr 9, 1981·Nature·S AndersonI G Young
Apr 1, 1995·Neurology·J J Barton
Mar 24, 1998·Annual Review of Medicine·C W Bazil, T A Pedley
Nov 3, 1998·European Journal of Biochemistry·W K PorteousM P Murphy
Apr 25, 2000·The EMBO Journal·H Schägger, K Pfeiffer
Apr 26, 2000·European Journal of Human Genetics : EJHG·J M van den OuwelandJ A Maassen
Jul 4, 2001·Pediatrics·D R NordliD C De Vivo
Sep 25, 2001·IUBMB Life·R L VeechG F Cahill
Jun 27, 2003·The New England Journal of Medicine·Salvatore DiMauro, Eric A Schon
Sep 30, 2003·Molecular & Cellular Proteomics : MCP·Daniel F BogenhagenRyuji Kobayashi
Nov 8, 2003·Nutrition Reviews·Theodore B VanItallie, Thomas H Nufert
Feb 12, 2004·Cancer Research·Rodrigue RossignolRoderick A Capaldi
Mar 30, 2004·Annals of Neurology·Patrick G SullivanJong M Rho

❮ Previous
Next ❯

Citations

Jun 20, 2007·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Hoon-Chul KangSi Houn Hahn
May 28, 2010·Journal of Inherited Metabolic Disease·Paul M Smith, Robert N Lightowlers
Jul 30, 2010·Journal of Inherited Metabolic Disease·Saskia Koene, Jan Smeitink
Nov 21, 2008·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Rita HorvathPatrick F Chinnery
Apr 30, 2005·Nature Reviews. Genetics·Robert W Taylor, Doug M Turnbull
Feb 20, 2010·Human Molecular Genetics·Sofia Ahola-ErkkiläAnu Suomalainen
Jun 12, 2010·Human Molecular Genetics·Emi OgasawaraJun-Ichi Hayashi
Jan 13, 2010·PloS One·Daniel J M Fernández-AyalaHoward T Jacobs
May 6, 2014·Revue neurologique·V ProcaccioP Reynier
Sep 24, 2005·Proceedings of the National Academy of Sciences of the United States of America·Maria Pilar Bayona-BafaluyCarlos T Moraes
Aug 1, 2014·Pediatric Neurology·Josef Finsterer, Sonam Kothari
Jan 19, 2010·Annual Review of Pathology·Douglas C WallaceVincent Procaccio
Feb 8, 2011·Nutrition Reviews·Manuel SchiffPierre Rustin
Jan 20, 2016·European Journal of Clinical Investigation·Ana F BrancoTeresa Cunha-Oliveira
Jun 25, 2008·The Journal of Cell Biology·Robert W GilkersonMercy M Davidson
Mar 11, 2005·Expert Opinion on Biological Therapy·Robert W Taylor
May 29, 2012·Trends in Endocrinology and Metabolism : TEM·Manuel SchiffPierre Rustin
Aug 30, 2011·Epilepsy Research·Adam L Hartman
Jun 18, 2010·Trends in Molecular Medicine·Eric A SchonRobert W Gilkerson
Oct 24, 2009·Epilepsy Research·Simon Waldbaum, Manisha Patel
Mar 10, 2009·Experimental Neurology·Alexei P KudinWolfram S Kunz
Oct 11, 2008·Brain Research Reviews·Marwan MaaloufMark P Mattson
Jan 31, 2012·Developmental Medicine and Child Neurology·Shamima Rahman
Oct 15, 2013·British Journal of Pharmacology·M KanabusS Rahman
Sep 8, 2010·Developmental Disabilities Research Reviews·Tina WenzCarlos T Moraes
Aug 1, 2006·Pediatric Neurology·Hoon-Chul KangSi Hoon Han
Jun 14, 2014·Pharmacology & Therapeutics·Christopher A ReidSteven Petrou
May 14, 2016·Clinical Nutrition : Official Journal of the European Society of Parenteral and Enteral Nutrition·Laurent BéghinDries Dobbelaere
May 9, 2007·Bioscience Reports·Salvatore DiMauro, Michelangelo Mancuso
May 12, 2007·Bioscience Reports·Julie L GardnerRobert W Taylor
Jun 26, 2015·Journal of Inherited Metabolic Disease·S Scholl-BürgiD Karall
May 13, 2015·Journal of Inherited Metabolic Disease·Shamima Rahman
Mar 15, 2015·Biochimica Et Biophysica Acta·Carlo ViscomiMassimo Zeviani
Nov 26, 2008·Biochimica Et Biophysica Acta·Salvatore Dimauro, Pierre Rustin
Aug 26, 2009·Communicative & Integrative Biology·Robert W Gilkerson, Eric A Schon
Jun 22, 2011·Neuron·Eric A Schon, Serge Przedborski
Jul 30, 2014·Frontiers in Pediatrics·Eleonora NapoliCecilia Giulivi
Aug 26, 2009·The International Journal of Biochemistry & Cell Biology·Robert W Gilkerson

❮ Previous
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