Acidosis overrides oxygen deprivation to maintain mitochondrial function and cell survival

Mireille Khacho, Michelle Tarabay, David Patten, Pamela Khacho, Jason G. MacLaurin, Jennifer Guadagno, Richard Bergeron, Sean P. Cregan, Mary-Ellen Harper, David S. Park and Ruth S. Slack ()
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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
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

Nature Communications, 2014, vol. 5, issue 1, 1-15

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms4550

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