Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland; Oroboros Instruments, Innsbruck, Austria; Corresponding author. Institut des Sciences du Sport de l’Université de Lausanne, Quartier UNIL-Centre, Bâtiment Synathlon, 1015, Lausanne, Switzerland.
Timea Komlódi
Oroboros Instruments, Innsbruck, Austria
Cristiane Cecatto
Oroboros Instruments, Innsbruck, Austria
Luiza H.D. Cardoso
Oroboros Instruments, Innsbruck, Austria
Anne-Claire Compagnion
Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland
Alessandro Matera
Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland
Daniele Tavernari
Department of Computational Biology, University of Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland; Swiss Cancer Centre Léman, Lausanne, Switzerland
Olivier Campiche
Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland
Rosa Chiara Paolicelli
Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland
Nadège Zanou
Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland
Bengt Kayser
Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland
Erich Gnaiger
Oroboros Instruments, Innsbruck, Austria
Nicolas Place
Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland
Mitochondrial respiration extends beyond ATP generation, with the organelle participating in many cellular and physiological processes. Parallel changes in components of the mitochondrial electron transfer system with respiration render it an appropriate hub for coordinating cellular adaption to changes in oxygen levels. How changes in respiration under functional hypoxia (i.e., when intracellular O2 levels limit mitochondrial respiration) are relayed by the electron transfer system to impact mitochondrial adaption and remodeling after hypoxic exposure remains poorly defined. This is largely due to challenges integrating findings under controlled and defined O2 levels in studies connecting functions of isolated mitochondria to humans during physical exercise. Here we present experiments under conditions of hypoxia in isolated mitochondria, myotubes and exercising humans. Performing steady-state respirometry with isolated mitochondria we found that oxygen limitation of respiration reduced electron flow and oxidative phosphorylation, lowered the mitochondrial membrane potential difference, and decreased mitochondrial calcium influx. Similarly, in myotubes under functional hypoxia mitochondrial calcium uptake decreased in response to sarcoplasmic reticulum calcium release for contraction. In both myotubes and human skeletal muscle this blunted mitochondrial adaptive responses and remodeling upon contractions. Our results suggest that by regulating calcium uptake the mitochondrial electron transfer system is a hub for coordinating cellular adaption under functional hypoxia.
