Energetic cost of the cross-talk between calcium dynamics and mitochondrial metabolism

Ion exchanges across mitochondrial membrane play a crucial role for energy metabolism [1–2]. In this work, we focus on the interplay between Ca2+ dynamics and mitochondrial metabolism. Ca2+ activates different enzymes of the TCA cycle and thereby enhances ATP production, while Ca2+ exchanges via SERCA and PMCA pumps are consuming ATP. The kinetics of this coupling has been studied with mathematical modelling [3–5], but its concrete energetic cost remains elusive. Here, we investigate this cost computationally by means of the entropy production rate (EPR) of Ca2+ exchanges and major mitochondrial metabolic processes. We show that the EPR as a measure for the throughput of the Gibbs free enthalpy of the TCA cycle exhibits a maximum in dependence on the glucose level, which could represent an optimal working regime of cells. 1. Wu, F. et al. J. Biol. Chem. 2007, 282, 24525–24537. 2. Wei, A.-C. et al. Biophys. J. 2011, 100, 2894–2903. 3. Magnus, G.; Keizer, J. Am. J. Physiol. 1998, 274, C1158-1173. 4. Bertram, R. et al. A. J. Theor. Biol. 2006, 243, 575–586. 5. Wacquier, B. et al. Sci. Rep. 2016, 6, 19316.