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Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS

Author

Listed:
  • Edward T. Chouchani

    (MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, UK
    University of Cambridge, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, UK)

  • Victoria R. Pell

    (University of Cambridge, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, UK)

  • Edoardo Gaude

    (MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Box 197, Cambridge Biomedical Campus, Cambridge CB2 0XZ, UK)

  • Dunja Aksentijević

    (King’s College London, British Heart Foundation Centre of Research Excellence, The Rayne Institute, St Thomas’ Hospital, London SE1 7EH, UK)

  • Stephanie Y. Sundier

    (University College London, Gower Street, London WC1E 6BT, UK)

  • Ellen L. Robb

    (MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, UK)

  • Angela Logan

    (MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, UK)

  • Sergiy M. Nadtochiy

    (University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, New York 14642, USA)

  • Emily N. J. Ord

    (Institute of Cardiovascular & Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK)

  • Anthony C. Smith

    (MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, UK)

  • Filmon Eyassu

    (MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, UK)

  • Rachel Shirley

    (Institute of Cardiovascular & Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK)

  • Chou-Hui Hu

    (University of Cambridge, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, UK)

  • Anna J. Dare

    (MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, UK)

  • Andrew M. James

    (MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, UK)

  • Sebastian Rogatti

    (MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, UK)

  • Richard C. Hartley

    (School of Chemistry, University of Glasgow, Glasgow G12 8QQ, UK)

  • Simon Eaton

    (Unit of Paediatric Surgery, UCL Institute of Child Health, London WC1N 1EH, UK)

  • Ana S. H. Costa

    (MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Box 197, Cambridge Biomedical Campus, Cambridge CB2 0XZ, UK)

  • Paul S. Brookes

    (University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, New York 14642, USA)

  • Sean M. Davidson

    (Hatter Cardiovascular Institute, University College London, 67 Chenies Mews, London WC1E 6HX, UK)

  • Michael R. Duchen

    (University College London, Gower Street, London WC1E 6BT, UK)

  • Kourosh Saeb-Parsy

    (Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK)

  • Michael J. Shattock

    (King’s College London, British Heart Foundation Centre of Research Excellence, The Rayne Institute, St Thomas’ Hospital, London SE1 7EH, UK)

  • Alan J. Robinson

    (MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, UK)

  • Lorraine M. Work

    (Institute of Cardiovascular & Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK)

  • Christian Frezza

    (MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Box 197, Cambridge Biomedical Campus, Cambridge CB2 0XZ, UK)

  • Thomas Krieg

    (University of Cambridge, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, UK)

  • Michael P. Murphy

    (MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, UK)

Abstract

A metabolomics study on the ischaemic heart identifies succinate as a metabolite that drives the production of reactive oxygen species and contributes to ischaemia-reperfusion injury; pharmacological inhibition of succinate accumulation ameliorates ischaemia-reperfusion injury in a mouse model of heart attack and a rat model of stroke.

Suggested Citation

  • Edward T. Chouchani & Victoria R. Pell & Edoardo Gaude & Dunja Aksentijević & Stephanie Y. Sundier & Ellen L. Robb & Angela Logan & Sergiy M. Nadtochiy & Emily N. J. Ord & Anthony C. Smith & Filmon Ey, 2014. "Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS," Nature, Nature, vol. 515(7527), pages 431-435, November.
    • Handle: RePEc:nat:nature:v:515:y:2014:i:7527:d:10.1038_nature13909
    DOI: 10.1038/nature13909
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    Cited by:

    1. Maithily S. Nanadikar & Ana M. Vergel Leon & Jia Guo & Gijsbert J. Belle & Aline Jatho & Elvina S. Philip & Astrid F. Brandner & Rainer A. Böckmann & Runzhu Shi & Anke Zieseniss & Carla M. Siemssen & , 2023. "IDH3γ functions as a redox switch regulating mitochondrial energy metabolism and contractility in the heart," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Pankaj Sharma & Elena Maklashina & Markus Voehler & Sona Balintova & Sarka Dvorakova & Michal Kraus & Katerina Hadrava Vanova & Zuzana Nahacka & Renata Zobalova & Stepana Boukalova & Kristyna Cunatova, 2024. "Disordered-to-ordered transitions in assembly factors allow the complex II catalytic subunit to switch binding partners," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
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    5. Xueqiang Wang & Xing Zhang & Ke Cao & Mengqi Zeng & Xuyang Fu & Adi Zheng & Feng Zhang & Feng Gao & Xuan Zou & Hao Li & Min Li & Weiqiang Lv & Jie Xu & Jiangang Long & Weijin Zang & Jinghai Chen & Fen, 2022. "Cardiac disruption of SDHAF4-mediated mitochondrial complex II assembly promotes dilated cardiomyopathy," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    6. Chris G. Faulkes & Thomas R. Eykyn & Jan Lj. Miljkovic & James D. Gilbert & Rebecca L. Charles & Hiran A. Prag & Nikayla Patel & Daniel W. Hart & Michael P. Murphy & Nigel C. Bennett & Dunja Aksentije, 2024. "Naked mole-rats have distinctive cardiometabolic and genetic adaptations to their underground low-oxygen lifestyles," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    7. John O. Onukwufor & M. Arsalan Farooqi & Anežka Vodičková & Shon A. Koren & Aksana Baldzizhar & Brandon J. Berry & Gisela Beutner & George A. Porter & Vsevolod Belousov & Alan Grossfield & Andrew P. W, 2022. "A reversible mitochondrial complex I thiol switch mediates hypoxic avoidance behavior in C. elegans," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    8. Xiaoduo Tang & Jingyan Ren & Xin Wei & Tao Wang & Haiqiu Li & Yihan Sun & Yang Liu & Mingli Chi & Shoujun Zhu & Laijin Lu & Junhu Zhang & Bai Yang, 2023. "Exploiting synergistic effect of CO/NO gases for soft tissue transplantation using a hydrogel patch," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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