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Acidosis overrides oxygen deprivation to maintain mitochondrial function and cell survival

Author

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  • Mireille Khacho

    (Faculty of Medicine, University of Ottawa)

  • Michelle Tarabay

    (Faculty of Medicine, University of Ottawa)

  • David Patten

    (Faculty of Medicine, University of Ottawa)

  • Pamela Khacho

    (Faculty of Medicine, University of Ottawa)

  • Jason G. MacLaurin

    (Faculty of Medicine, University of Ottawa)

  • Jennifer Guadagno

    (J. Allyn Taylor Centre for Cell Biology, Robarts Research Institute, The University of Western Ontario)

  • Richard Bergeron

    (Faculty of Medicine, University of Ottawa
    Ottawa Hospital Research Institute)

  • Sean P. Cregan

    (J. Allyn Taylor Centre for Cell Biology, Robarts Research Institute, The University of Western Ontario)

  • Mary-Ellen Harper

    (Microbiology and Immunology, University of Ottawa)

  • David S. Park

    (Faculty of Medicine, University of Ottawa)

  • Ruth S. Slack

    (Faculty of Medicine, University of Ottawa)

Abstract

Sustained cellular function and viability of high-energy demanding post-mitotic cells rely on the continuous supply of ATP. The utilization of mitochondrial oxidative phosphorylation for efficient ATP generation is a function of oxygen levels. As such, oxygen deprivation, in physiological or pathological settings, has profound effects on cell metabolism and survival. Here we show that mild extracellular acidosis, a physiological consequence of anaerobic metabolism, can reprogramme the mitochondrial metabolic pathway to preserve efficient ATP production regardless of oxygen levels. Acidosis initiates a rapid and reversible homeostatic programme that restructures mitochondria, by regulating mitochondrial dynamics and cristae architecture, to reconfigure mitochondrial efficiency, maintain mitochondrial function and cell survival. Preventing mitochondrial remodelling results in mitochondrial dysfunction, fragmentation and cell death. Our findings challenge the notion that oxygen availability is a key limiting factor in oxidative metabolism and brings forth the concept that mitochondrial morphology can dictate the bioenergetic status of post-mitotic cells.

Suggested Citation

  • Mireille Khacho & Michelle Tarabay & David Patten & Pamela Khacho & Jason G. MacLaurin & Jennifer Guadagno & Richard Bergeron & Sean P. Cregan & Mary-Ellen Harper & David S. Park & Ruth S. Slack, 2014. "Acidosis overrides oxygen deprivation to maintain mitochondrial function and cell survival," Nature Communications, Nature, vol. 5(1), pages 1-15, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4550
    DOI: 10.1038/ncomms4550
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    Cited by:

    1. Mathieu Ouellet & Gérald Guillebaud & Valerie Gervais & David Lupien St-Pierre & Marc Germain, 2017. "A novel algorithm identifies stress-induced alterations in mitochondrial connectivity and inner membrane structure from confocal images," PLOS Computational Biology, Public Library of Science, vol. 13(6), pages 1-23, June.
    2. Luca Simula & Mattia Fumagalli & Lene Vimeux & Irena Rajnpreht & Philippe Icard & Gary Birsen & Dongjie An & Frédéric Pendino & Adrien Rouault & Nadège Bercovici & Diane Damotte & Audrey Lupo-Mansuet , 2024. "Mitochondrial metabolism sustains CD8+ T cell migration for an efficient infiltration into solid tumors," Nature Communications, Nature, vol. 15(1), pages 1-23, December.

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