Cholesterol impairs the adenine nucleotide translocator-mediated mitochondrial permeability transition through altered membrane fluidity.

The Journal of Biological Chemistry
A ColellJose C Fernandez-Checa

Abstract

Mitochondrial permeability transition (MPT) has been proposed to play a key role in cell death. Downstream MPT events include the release of apoptogenic factors that sets in motion the mitochondrial apoptosome leading to caspase activation. The current work examined the regulation of MPT by membrane fluidity modulated upon cholesterol enrichment. Mitochondria enriched in cholesterol displayed increased microviscosity resulting in impaired MPT induced by atractyloside, a c-conformation stabilizing ligand of the adenine nucleotide translocator (ANT). This effect was dependent on the dose of cholesterol loaded and reversed upon the fluidization of mitochondria by the fatty acid derivative A2C. Mitoplasts derived from cholesterol-enriched mitochondria responded to atractyloside in a similar fashion as intact mitochondria, indicating that a significant amount of cholesterol is still found in the inner membrane. The effects of cholesterol on MPT induced by atractyloside were mirrored by the release of intermembrane proteins, cytochrome c, Smac/Diablo, and apoptosis inducing factor. However, cholesterol loading did not affect the uptake rate of adenine nucleotide hence dissociating the function of ANT as a MPT-mediated protein from it...Continue Reading

References

Jul 1, 1977·Biochemical Pharmacology·E R Gordon
Jun 2, 1979·Biochimica Et Biophysica Acta·K Hildenbrand, C Nicolau
Dec 1, 1977·Biochimica Et Biophysica Acta·E M KosowerP Wegman
Jul 1, 1968·The Journal of Cell Biology·C Schnaitman, J W Greenawalt
Jan 1, 1983·Alcoholism, Clinical and Experimental Research·C C CunninghamL L Rudel
Jul 17, 1995·Biochimica Et Biophysica Acta·M Zoratti, I Szabò
Oct 1, 1993·Journal of Bioenergetics and Biomembranes·M Klingenberg
Mar 15, 1996·The Journal of Biological Chemistry·B S KristalB P Yu
Sep 9, 1997·Biochemistry·G GimplF Fahrenholz
Aug 28, 1998·Science·D R Green, J C Reed
Sep 30, 1998·Cell·D R Green
Jan 20, 1999·The Journal of Experimental Medicine·S A SusinG Kroemer
Nov 24, 1999·Biochemical and Biophysical Research Communications·J G PastorinoJ B Hoek
Apr 27, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·C García-RuizJ C Fernández-Checa
May 5, 2000·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J G Pastorino, J B Hoek
May 10, 2000·Nature Medicine·G Kroemer, J C Reed
Sep 2, 2000·Science·C Brenner, G Kroemer
Apr 20, 2001·Proceedings of the National Academy of Sciences of the United States of America·E KojroF Fahrenholz
May 15, 2001·Biological Signals and Receptors·M M Sugrue, W G Tatton
Aug 3, 2001·The Journal of Biological Chemistry·B M PolsterG Fiskum

❮ Previous
Next ❯

Citations

Feb 2, 2010·Journal of Physiology and Biochemistry·I AlmansaF J Romero
Aug 7, 2008·Journal of Bioenergetics and Biomembranes·John G Pastorino, Jan B Hoek
May 4, 2012·Molecular Neurobiology·Gunter P EckertWalter E Muller
Sep 4, 2009·Archives of Pharmacal Research·Jung Rok LeeKwang Pyo Kim
Feb 12, 2005·Antioxidants & Redox Signaling·Alicia J Kowaltowski, Gary Fiskum
Oct 7, 2009·Antioxidants & Redox Signaling·Montserrat MaríJosé C Fernández-Checa
Apr 11, 2008·Journal of Gastroenterology and Hepatology·Anna FernándezJosé C Fernandez-Checa
Oct 5, 2006·BMC Cancer·Daniel PouliquenJean Menanteau
Apr 29, 2009·PloS One·Franziska B MullauerJan Paul Medema
Feb 21, 2014·Molecular Neurobiology·Xiaoguang YangJames C-M Lee
Nov 27, 2014·Journal of Bioenergetics and Biomembranes·Laura A MartinBarbara Karten
Jul 10, 2009·Archives of Toxicology·Tao Zeng, Ke-Qin Xie
Oct 27, 2009·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·Kenneth McMartin
Mar 27, 2013·Cancer Investigation·Gayatri SharmaNavneet Agnihotri
Sep 30, 2015·Free Radical Biology & Medicine·Annette Graham
Apr 25, 2009·Alcoholism, Clinical and Experimental Research·Anna FernándezJosé C Fernández-Checa
Jun 15, 2005·Biochimica Et Biophysica Acta·Fernanda RicchelliSergio Bova
Apr 23, 2005·Toxicology and Applied Pharmacology·Jose C Fernandez-Checa, Neil Kaplowitz
Feb 16, 2010·Biochimica Et Biophysica Acta·Joan MonteroJose C Fernández-Checa
Jun 2, 2015·Biochimica Et Biophysica Acta·Graciela ArguelloSilvana Zanlungo
Jun 16, 2015·Frontiers in Neuroscience·Donghui ZhuSholpan Askarova
Jun 5, 2015·Materials Science & Engineering. C, Materials for Biological Applications·Tingting ZhaoZhiwei Liu
Jun 30, 2012·The International Journal of Biochemistry & Cell Biology·Janett EckmannGunter P Eckert
Sep 18, 2012·Cell Reports·Bradley Smith, Hartmut Land
Sep 5, 2006·Cell Metabolism·Montserrat MaríCarmen García-Ruiz
Jul 3, 2016·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Cristiane CecattoMoacir Wajner
Jul 20, 2016·Molecular Nutrition & Food Research·Nina HirschOren Tirosh
Apr 6, 2017·International Journal of Rheumatic Diseases·Saba FarnaghiIndira Prasadam

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.