AMPK and PFKFB3 mediate glycolysis and survival in response to mitophagy during mitotic arrest

Nature Cell Biology
Elena DoménechMarcos Malumbres

Abstract

Blocking mitotic progression has been proposed as an attractive therapeutic strategy to impair proliferation of tumour cells. However, how cells survive during prolonged mitotic arrest is not well understood. We show here that survival during mitotic arrest is affected by the special energetic requirements of mitotic cells. Prolonged mitotic arrest results in mitophagy-dependent loss of mitochondria, accompanied by reduced ATP levels and the activation of AMPK. Oxidative respiration is replaced by glycolysis owing to AMPK-dependent phosphorylation of PFKFB3 and increased production of this protein as a consequence of mitotic-specific translational activation of its mRNA. Induction of autophagy or inhibition of AMPK or PFKFB3 results in enhanced cell death in mitosis and improves the anti-tumoral efficiency of microtubule poisons in breast cancer cells. Thus, survival of mitotic-arrested cells is limited by their metabolic requirements, a feature with potential implications in cancer therapies aimed to impair mitosis or metabolism in tumour cells.

References

Jul 6, 2000·Molecular Cell·S PyronnetN Sonenberg
Nov 28, 2002·Traffic·Eeva-Liisa EskelinenJohn M Lucocq
Jan 22, 2004·Biochemical and Biophysical Research Communications·Asish K SahaNeil B Ruderman
May 20, 2005·Nature·Tilman OltersdorfSaul H Rosenberg
Aug 24, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hidenori BandoTakao Koike
Aug 10, 2006·Nature Reviews. Molecular Cell Biology·Jan-Michael Peters
Feb 16, 2007·The Journal of Biological Chemistry·Naoko TaguchiKatsuyoshi Mihara
Apr 12, 2007·Nature Reviews. Molecular Cell Biology·Andrea Musacchio, Edward D Salmon
Sep 25, 2007·Cell Cycle·Ezgi TasdemirGuido Kroemer
Feb 13, 2008·Cell·Maria PiquéRaúl Méndez
May 3, 2008·Cancer Research·Christin TseSteven W Elmore
Jun 3, 2008·Biochimica Et Biophysica Acta·Ligia C Gomes, Luca Scorrano
Jul 5, 2008·Science·Satoshi TsukamotoNoboru Mizushima
Oct 8, 2008·Cell Cycle·Ezgi TasdemirGuido Kroemer
May 5, 2009·Cell Cycle·Leyuan LiuWallace L McKeehan
May 9, 2009·The Journal of Clinical Investigation·María SalazarGuillermo Velasco
May 23, 2009·Science·Matthew G Vander HeidenCraig B Thompson
Oct 6, 2009·Cancer Cell·Conly L Rieder, René H Medema
Oct 6, 2009·Cancer Cell·Hsiao-Chun HuangTimothy J Mitchison
Mar 31, 2010·The Journal of Cell Biology·Caoimhín G ConcannonJochen H M Prehn
Jun 29, 2010·Journal of the American Chemical Society·Scott A BradleyAndreas Kaerner
Oct 13, 2010·Molecular and Cellular Biology·Yves MatthessKlaus Strebhardt
Dec 24, 2010·Nature Reviews. Molecular Cell Biology·Richard J Youle, Derek P Narendra
Jan 25, 2011·Nature Cell Biology·Joungmok KimKun-Liang Guan
Apr 5, 2011·Cell Metabolism·Peiling TsouLewis C Cantley
Apr 30, 2011·Nature Reviews. Molecular Cell Biology·Ilio VitaleGuido Kroemer
Jun 8, 2011·Proceedings of the National Academy of Sciences of the United States of America·Angelika S RamboldJennifer Lippincott-Schwartz
Dec 6, 2011·Nature Medicine·Elena Ortiz-ZapaterPilar Navarro

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Citations

Mar 8, 2016·Ageing Research Reviews·Raquel Gómez-SintesPatricia Boya
Dec 30, 2015·Trends in Pharmacological Sciences·Biplab Dasgupta, Rishi Raj Chhipa
May 15, 2016·Experimental and Molecular Pathology·Haiyan XuFang Wang
May 21, 2016·Nature Reviews. Endocrinology·Miguel LópezCarlos Diéguez
Aug 12, 2016·Open Biology·Ailsa BennettStephen S Taylor
Aug 5, 2016·FEBS Letters·Helga Simon-MolasAnna Manzano
Oct 18, 2016·Trends in Cell Biology·María Salazar-Roa, Marcos Malumbres
Nov 2, 2016·The Journal of Clinical Investigation·Qingzhang ZhuAnutosh Chakraborty
Feb 18, 2017·Current Opinion in Hematology·Laure-Anne TeuwenPeter Carmeliet
Feb 25, 2017·European Journal of Endocrinology·Miguel López
Nov 21, 2017·The FEBS Journal·Catherine E RodgerIan G Ganley
Dec 22, 2017·Signal Transduction and Targeted Therapy·Linlin ShiWeidong Han
Sep 25, 2017·International Journal of Cancer. Journal International Du Cancer·Stefan Rodic, Mark David Vincent
Jul 13, 2018·European Journal of Clinical Investigation·Miguel López
Feb 13, 2018·Endocrine-related Cancer·Mark A WhiteDaniel E Frigo
Sep 28, 2018·Tissue Engineering. Part a·Lindsey T SaldinStephen F Badylak
Jan 23, 2019·Critical Reviews in Biochemistry and Molecular Biology·Shanmugasundaram Ganapathy-Kanniappan
Jul 10, 2019·EMBO Molecular Medicine·Seung Hee LeeJohn Hwa
Feb 21, 2018·EMBO Reports·Manuel HaschkaAndreas Villunger
May 4, 2017·The EMBO Journal·Lorena Esteban-MartínezPatricia Boya
Aug 25, 2016·Clinical Science·Pablo B Martínez de MorentinMiguel López
Feb 6, 2017·Oncotarget·Charlotte TaylorAhmed Ashour Ahmed
May 6, 2020·Antioxidants·Sanja MijatovićDanijela Maksimović-Ivanić
Apr 5, 2019·Oncology Letters·Lin Jin, Yanhong Zhou
Sep 15, 2020·The Journal of Cell Biology·Samuel A KillackeyStephen E Girardin
Apr 24, 2019·Geriatrics·Kyle DammannChristoph Gasche
Feb 9, 2017·Nature Reviews. Urology·Ayesha S Khan, Daniel E Frigo
Nov 21, 2018·Frontiers in Immunology·Farhan BasitI Jolanda M de Vries

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