Donnelly 2023 MitoFit
|Donnelly C, Komlódi T, Cecatto C, Cardoso LHD, Compagnion AC, Matera A, Tavernari D, Zanou N, Kayser B, Gnaiger E, Place N (2023) Functional hypoxia reduces mitochondrial calcium uptake. MitoFit Preprints 2023.2. https://doi.org/10.26124/mitofit:2023-0002|
» MitoFit Preprints 2023.2.
Donnelly Chris, Komlodi Timea, Cecatto Cristiane, Cardoso Luiza HD, Compagnion Anne-Claire, Matera Alessandro, Tavernari Daniele, Zanou Nadege, Kayser Bengt, Gnaiger Erich, Place Nicolas (2023) MitoFit Prep
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.
• Keywords: respirometry; membrane potential; skeletal muscle; exercise; coenzyme Q • Bioblast editor: Tindle-Solomon L • O2k-Network Lab: AT Innsbruck Oroboros, CH Lausanne Place N, HU Budapest Tretter L
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style
Stress:Hypoxia Organism: Human, Mouse Tissue;cell: Heart, Skeletal muscle, Nervous system, Other cell lines Preparation: Isolated mitochondria
Regulation: Calcium, mt-Membrane potential, Redox state
HRR: Oxygraph-2k, TIP2k, O2k-Fluorometer, Ca, NextGen-O2k