Difference between revisions of "Donnelly 2024 Redox Biol"

Revision as of 11:49, 25 February 2024

Donnelly C, Komlódi T, Cecatto C, Cardoso LHD, Compagnion A-C, Matera A, Tavernari D, Campiche O, Paolicelli RC, Zanou N, Kayser B, Gnaiger E, Place N (2024) Functional hypoxia reduces mitochondrial calcium uptake. Redox Biol 71:103037. https://doi.org/10.1016/j.redox.2024.103037

» Open Access

Donnelly Chris, Komlodi Timea, Cecatto Cristiane, Cardoso Luiza HD, Compagnion Anne-Claire, Matera Alessandro, Tavernari Daniele, Campiche Olivier, Paolicelli Rosa Chiara, Zanou Nadege, Kayser Bengt, Gnaiger Erich, Place Nicolas (2024) Redox Biol

Abstract: 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.

• Bioblast editor: Gnaiger E • O2k-Network Lab: AT Innsbruck Oroboros, CH Lausanne Place N

Labels: MiParea: Respiration, Exercise physiology;nutrition;life style

Stress:Hypoxia Organism: Human, Mouse Tissue;cell: Heart, Skeletal muscle Preparation: Intact organism, Isolated mitochondria, Intact cells

Regulation: Calcium, mt-Membrane potential, Oxygen kinetics, Redox state Coupling state: LEAK, OXPHOS, ET Pathway: N, S, NS, ROX HRR: Oxygraph-2k, O2k-Fluorometer, Ca, NextGen-O2k

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 |title=Donnelly C, Komlódi T, Cecatto C, Cardoso LHD, Compagnion A-C, Matera A, Tavernari D, Campiche O, Paolicelli RC, Zanou N, Kayser B, Gnaiger E, Place N (2024) Functional hypoxia reduces mitochondrial calcium uptake. Redox Biol 71:103037. https://doi.org/10.1016/j.redox.2024.103037
 |info=[https://www.sciencedirect.com/science/article/pii/S2213231724000132?via%3Dihub Open Access]
-|authors=Donnelly Chris, Komlodi Timea, Cecatto Cristiane, Cardoso Luiza HD, Compagnion Anne-Claire, Matera Alessandro, Tavernari Daniele, Campiche Olivier, Paolicelli Rosa Chiara, Zanou Nadège, Kayser Bengt, Gnaiger Erich, Place Nicolas
+|authors=Donnelly Chris, Komlodi Timea, Cecatto Cristiane, Cardoso Luiza HD, Compagnion Anne-Claire, Matera Alessandro, Tavernari Daniele, Campiche Olivier, Paolicelli Rosa Chiara, Zanou Nadege, Kayser Bengt, Gnaiger Erich, Place Nicolas
 |year=2024
 |journal=Redox Biol
-|abstract=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.
+|abstract=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 O<sub>2</sub> 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 O<sub>2</sub> 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.
 |editor=Gnaiger E
 |mipnetlab=AT Innsbruck Oroboros, CH Lausanne Place N