20.500.12556/DiRROS-20828 Mitochondria can substitute for parvalbumin to lowercytosolic calcium levels in the murine fast skeletal muscle Aim: Parvalbumin (PV) is a primary calcium buffer in mouse fast skeletal musclefibers. Previous work showed that PV ablation has a limited impact on cytosolicCa2+ ([Ca2+]cyto) transients and contractile response, while it enhances mitochon-drial density and mitochondrial matrix-free calcium concentration ([Ca2+]mito).Here, we aimed to quantitatively test the hypothesis that mitochondria act tocompensate for PV deficiency.Methods: We determined the free Ca 2+ redistribution during a 2 s 60 Hz tetanicstimulation in the sarcoplasmic reticulum, cytosol, and mitochondria. Via a re-action–diffusion Ca 2+ model, we quantitatively evaluated mitochondrial uptakeand storage capacity requirements to compensate for PV lack and analyzed pos-sible extracellular export.Results: [Ca 2+]mito during tetanic stimulation is greater in knock-out (KO)(1362 ± 392 nM) than in wild-type (WT) (855 ± 392 nM), p < 0.05. Under the as-sumption of a non-linear intramitochondrial buffering, the model predicts an ac-cumulation of 725 μmoles/Lfiber (buffering ratio 1:11 000) in KO, much higherthan in WT (137 μmoles/Lfiber, ratio 1:4500). The required transport rate via mi-tochondrial calcium uniporter (MCU) reaches 3 mM/s, compatible with availableliterature. TEM images of calcium entry units and Mn2+ quenching showed a greater capacity of store- operated calcium entry in KO compared to WT. However,levels of [Ca 2+]cyto during tetanic stimulation were not modulated to variations ofextracellular calcium.Conclusions: The model-based analysis of experimentally determined calciumdistribution during tetanic stimulation showed that mitochondria can act as abuffer to compensate for the lack of PV. This result contributes to a better under-standing of mitochondria's role in modulating [Ca2+]cyto in skeletal muscle fibers. calcium mitochondria mouse skeletal muscle fibers parvalbumin reaction-diffusion model kalcij mitohondriji mišična vlakna skeletnih mišic miši parvalbumin reaction–diffusion model true false true Angleški jezik Slovenski jezik © 2024 The Author(s) Neznano 2024-11-13 11:20:42 2024-11-13 11:20:42 2024-12-10 11:41:02 0000-00-00 00:00:00 2024 0 0 Opis vira z dne 13. 11. 2024; Nasl. z nasl. zaslona; str. 1-14 ǂiss.ǂ9 Vol. 240 2024 0000-00-00 Zaloznikova NiDoloceno NiDoloceno 2024-07-09 2024-07-15 2024-07-30 612 1748-1716 10.1111/apha.14208 214814467 24_11_13_101_Reggiani_214814467.pdf 24_11_13_101_Reggiani_214814467.pdf 1 444CDA853D07DE6199EF14F51714D3ED 56f86ba00b176ab00fa45f39a248015efbbe0e4c2baa8f33f1918da0358fdf50 3180270f-a1a9-11ef-ba3f-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=29407 https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14208 1 f157d0d6-a1a8-11ef-ba3f-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=29405 Znanstveno-raziskovalno središče Koper / Centro di Ricerche Scientifiche Capodistria 0 0 0