Calcium oscillations optimize the energetic efficiency of mitochondrial metabolism.

Biological sciences; Human metabolism; Molecular biology; Natural sciences; Multidisciplinary; Calcium signalling; Mitochondrial metabolism; Computational modelling

Abstract :

[en] 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.

Disciplines :

Physical, chemical, mathematical & earth Sciences: Multidisciplinary, general & others

Author, co-author :

VOORSLUIJS, Valerie ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Integrative Cell Signalling

AVANZINI, Francesco ; University of Luxembourg > Faculty of Science, Technology and Medicine > Department of Physics and Materials Science > Team Massimiliano ESPOSITO ; Department of Chemical Sciences, University of Padova, 1 Via F. Marzolo, 35131 Padova, Italy

FALASCO, Gianmaria ; University of Luxembourg > Faculty of Science, Technology and Medicine > Department of Physics and Materials Science > Team Massimiliano ESPOSITO ; Department of Physics and Astronomy, University of Padova, 8 Via F. Marzolo, 35131 Padova, Italy

ESPOSITO, Massimiliano ; University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Physics and Materials Science (DPHYMS)

SKUPIN, Alexander ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Integrative Cell Signalling ; Department of Neuroscience, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093, USA

External co-authors :

yes

Language :

English

Title :

Calcium oscillations optimize the energetic efficiency of mitochondrial metabolism.

Publication date :

15 March 2024

Journal title :

iScience

eISSN :

2589-0042

Publisher :

Elsevier Inc., United States

Volume :

Issue :

Pages :

109078

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://api.elsevier.com/content/article/PII:S2589004224002992?httpAccept=text/xml

Funders :

University of Luxembourg
National Research Fund

Funding text :

V.V. is funded by the Complex Living Systems Initiative at the University of Luxembourg . F.A. and M.E. are funded by the Luxembourg National Research Fund , grant ChemComplex ( C21/MS/16356329 ). G.F. is funded by the European Union – NextGenerationEU – and by the program STARS@UNIPD with project “ThermoComplex”. F.A., A.S., and M.E. acknowledge financial support of the Institute for Advanced Studies of the University of Luxembourg through an Audacity Grant ( IDAE-2020 ). The experiments presented in this paper were carried out using the HPC facilities of the University of Luxembourg 84 – see hpc.uni.lu .

Available on ORBilu :

since 01 March 2024

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