FKBP12-rapamycin-associated protein associates with mitochondria and senses osmotic stress via mitochondrial dysfunction

Proceedings of the National Academy of Sciences of the United States of America
Bimal N DesaiStuart L Schreiber

Abstract

FKBP12-rapamycin associated protein (FRAP, also known as mTOR or RAFT) is the founding member of the phosphatidylinositol kinase-related kinase family and functions as a sensor of physiological signals that regulate cell growth. Signals integrated by FRAP include nutrients, cAMP levels, and osmotic stress, and cellular processes affected by FRAP include transcription, translation, and autophagy. The mechanisms underlying the integration of such diverse signals by FRAP are largely unknown. Recently, FRAP has been reported to be regulated by mitochondrial dysfunction and depletion of ATP levels. Here we show that exposure of cells to hyperosmotic conditions (and to glucose-deficient growth medium) results in rapid and reversible dissipation of the mitochondrial proton gradient. These results suggest that the ability of FRAP to mediate osmotic stress response (and glucose deprivation response) is by means of an intermediate mitochondrial dysfunction. We also show that in addition to cytosolic FRAP a large portion of FRAP associates with the mitochondrial outer membrane. The results support the existence of a stress-sensing module consisting of mitochondria and mitochondrial outer membrane-associated FRAP. This module allows the ce...Continue Reading

References

Oct 5, 1995·Nature·E J BrownS L Schreiber
Dec 5, 1995·Proceedings of the National Academy of Sciences of the United States of America·L CheathamJ Blenis
Jan 1, 1995·Methods in Enzymology·M ReersL B Chen
Apr 14, 1999·Proceedings of the National Academy of Sciences of the United States of America·R T PetersonS L Schreiber
Aug 13, 1999·Genes & Development·A GrossS J Korsmeyer
Aug 24, 1999·The Journal of Biological Chemistry·L A Parrott, D J Templeton
Nov 1, 2000·Cell·T Schmelzle, M N Hall
Nov 3, 2001·Science·P B DennisG Thomas

❮ Previous
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Citations

May 3, 2013·Cell and Tissue Research·Stana Helena Giorgi GrossoM Mitzi Brentani
Aug 3, 2005·Nature Reviews. Microbiology·Donald L Nuss
Feb 1, 2003·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Naoki KimuraKazuyoshi Yonezawa
Sep 18, 2008·Proceedings of the National Academy of Sciences of the United States of America·Antonio BarquillaMiguel Navarro
Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Arvind Ramanathan, Stuart L Schreiber
Jul 16, 2013·Proceedings of the National Academy of Sciences of the United States of America·Charles BetzMichael N Hall
Sep 4, 2009·The Journal of Biological Chemistry·Ganna PanasyukIvan Gout
May 25, 2010·The Journal of Biological Chemistry·Teresa Cristina Leandro de JesusSergio Schenkman
Jul 29, 2008·The Journal of Biological Chemistry·Dongzhu MaYu Jiang
Dec 16, 2004·Molecular & Cellular Proteomics : MCP·Karim RezaulDavid Han
Mar 20, 2010·Lymphatic Research and Biology·Arnold S Kristof
Jan 12, 2007·Molecular Biology of the Cell·Xiangyu Liu, X F Steven Zheng
Dec 9, 2010·Journal of Molecular Cell Biology·Xuemin Wang, Christopher G Proud
Jun 25, 2009·Current Opinion in Rheumatology·Andras PerlPaul E Phillips
Dec 20, 2013·Open Biology·Marlous J Groenewoud, Fried J T Zwartkruis
Jul 19, 2003·Genes & Development·Ken InokiKun-Liang Guan
Jun 1, 2006·Acta Physiologica·F SchliessD Häussinger
Dec 12, 2003·Science's STKE : Signal Transduction Knowledge Environment·Thurl E Harris, John C Lawrence
Apr 10, 2003·Eukaryotic Cell·Karine DementhonCorinne Clavé
Jun 2, 2006·Molecular and Cellular Biology·Xingming DengW Stratford May
Apr 13, 2012·International Journal of Cell Biology·Hidemi Rikiishi
Nov 8, 2008·Circulation Research·Glenn Marsboom, Stephen L Archer
Nov 4, 2006·Biological Chemistry·Stefan M Schieke, Toren Finkel
May 20, 2006·Neurosurgical Focus·Florence Lefranc, Robert Kiss
Apr 7, 2011·Experimental & Molecular Medicine·Chang Hoon Cho
Apr 16, 2013·Antioxidants & Redox Signaling·Demet Candas, Jian Jian Li
May 11, 2005·Proceedings of the National Academy of Sciences of the United States of America·Michael W XieJing Huang
May 16, 2014·Bulletin of Experimental Biology and Medicine·N S ZaitsevaV A Starostenko
Jan 8, 2014·Molecular Neurobiology·Ting LiZhiping Hu
Nov 21, 2012·Biochimica Et Biophysica Acta·Robyn D Moir, Ian M Willis
Oct 9, 2013·Nature Reviews. Rheumatology·Andras Perl
Oct 14, 2009·Cellular and Molecular Life Sciences : CMLS·Xiaochun Bai, Yu Jiang
Jun 24, 2008·Scandinavian Journal of Gastroenterology·Ming-Ling ChangDeng-Yn Lin
Jan 5, 2014·The Journal of Cell Biology·Charles Betz, Michael N Hall
Dec 25, 2015·Nature Reviews. Rheumatology·Andras Perl
Feb 13, 2016·Frontiers in Physiology·Rebeca C Kalamgi, Lars Larsson
Jan 20, 2010·FEBS Letters·Chang Hwa JungDo-Hyung Kim

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