Rheb and mammalian target of rapamycin in mitochondrial homoeostasis

Open Biology
Marlous J Groenewoud, Fried J T Zwartkruis


Mitochondrial dysfunction has been associated with various diseases, such as cancer, myopathies, neurodegeneration and obesity. Mitochondrial homoeostasis is achieved by mechanisms that adapt the number of mitochondria to that required for energy production and for the supply of metabolic intermediates necessary to sustain cell growth. Simultaneously, mitochondrial quality control mechanisms are in place to remove malfunctioning mitochondria. In the cytoplasm, the protein complex mTORC1 couples growth-promoting signals with anabolic processes, in which mitochondria play an essential role. Here, we review the involvement of mTORC1 and Rheb in mitochondrial homoeostasis. The regulatory processes downstream of mTORC1 affect the glycolytic flux and the rate of mitophagy, and include regulation of the transcription factors HIF1α and YY1/PGC-1α. We also discuss how mitochondrial function feeds back on mTORC1 via reactive oxygen species signalling to adapt metabolic processes, and highlight how mTORC1 signalling is integrated with the unfolded protein response in mitochondria, which in Caenorhabditis elegans is mediated via transcription factors such as DVE-1/UBL-5 and ATFS-1.


Nov 3, 2001·Science·P B DennisGeorge Thomas
Apr 4, 2002·Proceedings of the National Academy of Sciences of the United States of America·Bimal N DesaiStuart L Schreiber
Jun 25, 2002·Genes & Development·Diane C FingarJohn Blenis
Jul 23, 2002·Molecular Biology of the Cell·Aimee L Edinger, Craig B Thompson
Aug 13, 2002·Nature Cell Biology·Christopher J PotterTian Xu
Aug 29, 2002·The EMBO Journal·Quan ZhaoNicholas J Hoogenraad
Nov 22, 2002·Proceedings of the National Academy of Sciences of the United States of America·Haihong ZongGerald I Shulman
May 29, 2003·Nature Cell Biology·Yong ZhangDuojia Pan
Jul 19, 2003·Genes & Development·Ken InokiKun-Liang Guan
Sep 6, 2003·Cancer Cell·James B BrugarolasWilliam G Kaelin
Apr 8, 2004·Molecular Cell·Ronald A Butow, Narayan G Avadhani
Jul 21, 2004·Cancer Cell·Reuben J ShawLewis C Cantley
Aug 11, 2004·Molecular Aspects of Medicine·Michael R Duchen
Sep 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Philippe P RouxJohn Blenis
Nov 13, 2004·The EMBO Journal·Marieke A G EssersBoudewijn M T Burgering
Jan 6, 2005·The Journal of Biological Chemistry·Michael N CorradettiKun-Liang Guan
Jul 29, 2005·The Journal of Biological Chemistry·Maya P ByfieldJonathan M Backer
Aug 2, 2005·Cell Metabolism·Jiandie LinBruce M Spiegelman
Sep 24, 2005·Proceedings of the National Academy of Sciences of the United States of America·Takahiro NobukuniGeorge Thomas
Sep 27, 2005·The Journal of Biological Chemistry·Dos D Sarbassov, David M Sabatini
Feb 18, 2006·Molecular Cell·Liping LiuM Celeste Simon
Jun 15, 2006·Annual Review of Genetics·Zhengchang Liu, Ronald A Butow
Jul 19, 2006·The Journal of Biological Chemistry·Stefan M SchiekeToren Finkel
Jan 27, 2007·The Biochemical Journal·Greg M FindlayRichard F Lamb
May 16, 2007·The Journal of Biological Chemistry·Stephen C Land, Andrew R Tee
Jun 21, 2007·The Journal of Biological Chemistry·Serhiy PankivTerje Johansen
Aug 23, 2007·Nature Reviews. Molecular Cell Biology·D Grahame Hardie
Oct 11, 2007·Developmental Cell·Cole M HaynesDavid Ron
Oct 12, 2007·The Journal of Biological Chemistry·Yong LiKun-Liang Guan
Dec 1, 2007·Proceedings of the National Academy of Sciences of the United States of America·Rachel L SchweersPaul A Ney
Jan 17, 2008·Genes & Development·Maurice Phillip DeYoungLeif W Ellisen
Jan 26, 2008·Cell Death and Differentiation·T Klimova, Navdeep S Chandel
Feb 13, 2008·Molecular and Cellular Biology·Tae YamamotoMasayuki Yamamoto
Apr 5, 2008·Current Opinion in Genetics & Development·Ralph J DeberardinisCraig B Thompson
Apr 29, 2008·Molecular Cell·Dana M GwinnReuben J Shaw
May 24, 2008·Science·Yasemin SancakDavid M Sabatini
Nov 26, 2008·The Journal of Cell Biology·Derek P NarendraRichard J Youle
Mar 3, 2009·Molecular Cell·Vladimir KirkinTerje Johansen
Mar 10, 2009·Free Radical Biology & Medicine·Brooke M EmerlingNavdeep S Chandel
Jul 9, 2009·Physiological Reviews·Marc LiesaAntonio Zorzano
Nov 18, 2009·Proceedings of the National Academy of Sciences of the United States of America·Tina WenzCarlos T Moraes
Dec 17, 2009·The Journal of Cell Biology·Valérie RissonYann-Gaël Gangloff
Dec 23, 2009·Nature Reviews. Molecular Cell Biology·Laura R PearceDario R Alessi
Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Arvind Ramanathan, Stuart L Schreiber
Jan 26, 2010·Nature Cell Biology·Sven GeislerWolfdieter Springer
Mar 17, 2010·Molecular Cell·Lijun YanRichard F Lamb
May 29, 2010·Science·Ryan J O DowlingNahum Sonenberg
Jul 31, 2010·Molecular Cell·Katrin DüvelBrendan D Manning
Nov 13, 2010·The Journal of Biological Chemistry·Audrey CarrierePhilippe P Roux
Dec 16, 2010·Nature Reviews. Molecular Cell Biology·Roberto ZoncuDavid M Sabatini
Dec 24, 2010·Nature Reviews. Molecular Cell Biology·Richard J Youle, Derek P Narendra
Feb 15, 2011·Genes & Development·Jessie Yanxiang GuoEileen White
Feb 18, 2011·The EMBO Journal·D Grahame Hardie
Apr 14, 2011·Journal of Cell Science·Luena Papa, Doris Germain
May 10, 2011·Annual Review of Biochemistry·Joungmok Kim, Kun-Liang Guan
May 27, 2011·American Journal of Physiology. Renal Physiology·Carolyn L BullerFrank C Brosius
Aug 13, 2011·The Journal of Biological Chemistry·Toren Finkel
Sep 6, 2011·Nature Cell Biology·Maria M Mihaylova, Reuben J Shaw
Sep 20, 2011·Journal of Cellular Physiology·Sébastien MichelPatricia Renard
Oct 11, 2011·Molecular Cell·Angeles DuranMaria T Diaz-Meco
Nov 15, 2011·Cell·Jorge Moscat, Maria T Diaz-Meco
Dec 24, 2011·Science·Giuseppe LiaJean-François Allemand
Jul 4, 2012·Molecular Cell·Raúl V DuránMichael N Hall
Sep 1, 2012·Science·Anthony A Hyman, Kai Simons
Nov 15, 2012·The EMBO Journal·Werner J H KoopmanPeter H G M Willems
Jan 18, 2013·Nature Reviews. Molecular Cell Biology·Astrid Eijkelenboom, Boudewijn M T Burgering
Mar 20, 2013·Proceedings of the National Academy of Sciences of the United States of America·Evelyn S VincowLeo J Pallanck
Apr 23, 2013·Cell Metabolism·Su MelserGiovanni Bénard
May 24, 2013·Nature·Riekelt H HoutkooperJohan Auwerx


Jan 7, 2016·Small GTPases·Amanda GarridoNabil Djouder
Aug 4, 2015·Biological & Pharmaceutical Bulletin·Satoru Kobayashi
Nov 22, 2015·British Medical Bulletin·P K RaiD M Turnbull
Jun 2, 2014·Amino Acids·Alfred J MeijerPatrice Codogno
May 17, 2015·Biochimica Et Biophysica Acta·Andrea Ruetenik, Antoni Barrientos
Feb 6, 2015·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Akira DoiReiko Sugiura
Mar 8, 2014·Experimental Gerontology·Eva Diana RunkelEkkehard Schulze
Nov 25, 2014·Cell·Cancer Genome Atlas Research Network
May 29, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·R Pinto-LeiteL Santos
Jan 24, 2019·Cellular and Molecular Life Sciences : CMLS·Yinxing MaSvetlana Dokudovskaya
Jan 19, 2019·Molecular Genetics and Genomics : MGG·Muhammad-Kashif ZahoorJacques Montagne
Apr 30, 2019·Journal of Cellular Physiology·Sugandh SaxenaPoonam Kakkar
Aug 15, 2017·Nature Reviews. Nephrology·Pallavi Bhargava, Rick G Schnellmann
Jan 11, 2018·Science Signaling·Ji-Hoon LeeTanya T Paull
Oct 6, 2016·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Binod KumarAkhil C Banerjea
Aug 14, 2015·Physiological Reviews·Joël Bockaert, Philippe Marin
Jul 25, 2019·Frontiers in Immunology·Alicia R WatsonAngus W Thomson

Methods Mentioned

nucleotide exchange
protein folding

Related Concepts

MTORC1 complex, rat
Transcription Factor
Signal Transduction
Caenorhabditis elegans
Reactive Oxygen Species
Mitochondrial Proteins

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