Calcium oscillations optimize the energetic efficiency of mitochondrial metabolism
Valérie Voorsluijs,
Francesco Avanzini,
Gianmaria Falasco,
Massimiliano Esposito,
Alexander Skupin
Affiliations
Valérie Voorsluijs
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 avenue du Swing, 4367 Belvaux, Luxembourg; Complex Systems and Statistical Mechanics, Department of Physics and Materials Science, University of Luxembourg, 162 A avenue de la Faïencerie, 1511 Luxembourg, Luxembourg; Corresponding author
Francesco Avanzini
Complex Systems and Statistical Mechanics, Department of Physics and Materials Science, University of Luxembourg, 162 A avenue de la Faïencerie, 1511 Luxembourg, Luxembourg; Department of Chemical Sciences, University of Padova, 1 Via F. Marzolo, 35131 Padova, Italy; Corresponding author
Gianmaria Falasco
Complex Systems and Statistical Mechanics, Department of Physics and Materials Science, University of Luxembourg, 162 A avenue de la Faïencerie, 1511 Luxembourg, Luxembourg; Department of Physics and Astronomy, University of Padova, 8 Via F. Marzolo, 35131 Padova, Italy; Corresponding author
Massimiliano Esposito
Complex Systems and Statistical Mechanics, Department of Physics and Materials Science, University of Luxembourg, 162 A avenue de la Faïencerie, 1511 Luxembourg, Luxembourg; Corresponding author
Alexander Skupin
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 avenue du Swing, 4367 Belvaux, Luxembourg; Department of Physics and Materials Science, University of Luxembourg, 162 A avenue de la Faïencerie, 1511 Luxembourg, Luxembourg; Department of Neuroscience, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093, USA; Corresponding author
Summary: Energy transduction is central to living organisms, but the impact of enzyme regulation and signaling on its thermodynamic efficiency is generally overlooked. Here, we analyze the efficiency of ATP production by the tricarboxylic acid cycle and oxidative phosphorylation, which generate most of the chemical energy in eukaryotes. Calcium signaling regulates this pathway and can affect its energetic output, but the concrete energetic impact of this cross-talk remains elusive. Calcium enhances ATP production by activating key enzymes of the tricarboxylic acid cycle while calcium homeostasis is ATP-dependent. We propose a detailed kinetic model describing the calcium-mitochondria cross-talk and analyze it using nonequilibrium thermodynamics: after identifying the effective reactions driving mitochondrial metabolism out of equilibrium, we quantify the mitochondrial thermodynamic efficiency for different conditions. Calcium oscillations, triggered by extracellular stimulation or energy deficiency, boost the thermodynamic efficiency of mitochondrial metabolism, suggesting a compensatory role of calcium signaling in mitochondrial bioenergetics.
