Endoplasmic reticulum stress-mediated mitochondrial dysfunction in aged hearts

Biochimica Et Biophysica Acta. Molecular Basis of Disease
Qun ChenEdward J Lesnefsky

Abstract

Aging impairs the mitochondrial electron transport chain (ETC), especially in interfibrillar mitochondria (IFM). Mitochondria are in close contact with the endoplasmic reticulum (ER). Induction of ER stress leads to ETC injury in adult heart mitochondria. We asked if ER stress contributes to the mitochondrial dysfunction during aging. Subsarcolemmal mitochondria (SSM) and IFM were isolated from 3, 18, and 24 mo. C57Bl/6 mouse hearts. ER stress progressively increased with age, especially in 24 mo. mice that manifest mitochondrial dysfunction. OXPHOS was decreased in 24 mo. IFM oxidizing complex I and complex IV substrates. Proteomic analysis showed that the content of multiple complex I subunits was decreased in IFM from 24 mo. hearts, but remained unchanged in in 18 mo. IFM without a decrease in OXPHOS. Feeding 24 mo. old mice with 4-phenylbutyrate (4-PBA) for two weeks attenuated the ER stress and improved mitochondrial function. These results indicate that ER stress contributes to the mitochondrial dysfunction in aged hearts. Attenuation of ER stress is a potential approach to improve mitochondrial function in aged hearts.

References

Jan 8, 1999·Biochemical and Biophysical Research Communications·J L LoeffenJ A Smeitink
Dec 22, 1999·Archives of Biochemistry and Biophysics·S W FanninC L Hoppel
Dec 22, 1999·Trends in Cell Biology·M F BauerM Brunner
Mar 22, 2003·Circulation Research·Sawa KostinJutta Schaper
May 15, 2003·Archives of Biochemistry and Biophysics·Shadi MoghaddasEdward J Lesnefsky
Jul 3, 2003·Biochimica Et Biophysica Acta·Judy HirstJohn E Walker
Jul 4, 2003·The Journal of Biological Chemistry·Qun ChenEdward J Lesnefsky
Jul 19, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jinping LiRoger H Unger
Apr 2, 2004·The Journal of Biological Chemistry·Ruming ChenJohn E Walker
Sep 22, 2005·The Journal of Pharmacology and Experimental Therapeutics·Qun ChenEdward J Lesnefsky
Dec 24, 2005·The Biochemical Journal·Lindsay S BurwellPaul S Brookes
Jun 23, 2006·American Journal of Physiology. Cell Physiology·David D ArringtonRick G Schnellmann
Jun 24, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Edward J LesnefskyCharles L Hoppel
Jan 4, 2007·The Journal of Clinical Investigation·Victoria Del Gaizo MooreAnthony Letai
Jul 25, 2007·Journal of Biochemistry·Taku OzakiSei-Ichi Ishiguro
Aug 8, 2007·The Journal of Experimental Medicine·Sruti ShivaMark T Gladwin
Nov 17, 2007·Cardiovascular Research·Asa B Gustafsson, Roberta A Gottlieb
Dec 9, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Erinne R DabkowskiJohn M Hollander
Dec 26, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Imran N MungrueAldons J Lusis
Mar 4, 2009·Journal of Molecular and Cellular Cardiology·Melanie PaillardMichel Ovize
Jul 7, 2009·The International Journal of Biochemistry & Cell Biology·Dirk Schiller
Oct 10, 2009·Nature Protocols·Mariusz R WieckowskiPaolo Pinton
Jan 8, 2010·Human Molecular Genetics·Devanjan SinhaPatrick D'Silva
Oct 30, 2010·Circulation Research·Tetsuo MinaminoMasafumi Kitakaze
Oct 4, 2011·Journal of Cardiovascular Pharmacology·Qun ChenEdward J Lesnefsky
May 15, 2013·Molecular Medicine·Dana MarcusHaya Lorberboum-Galski
Dec 10, 2013·Experimental Gerontology·Jason N PeartJohn P Headrick
Apr 4, 2014·American Journal of Physiology. Cell Physiology·Aijun XuEdward J Lesnefsky
Oct 7, 2014·Biochimica Et Biophysica Acta·Ana C MoreiraVilma A Sardão

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Aging (Keystone)

This feed focuses on cellular aging with emphasis on the mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.

Cell Aging

This feed focuses on cellular aging with emphasis on mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.