| Title: | Mitochondria can substitute for parvalbumin to lowercytosolic calcium levels in the murine fast skeletal muscle |
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| Authors: | ID Marcucci, Lorenzo (Author)
ID Nogara, Leonardo (Author)
ID Canato, Marta (Author)
ID Germinario, Elena (Author)
ID Raffaello, Anna (Author)
ID Carraro, Michela (Author)
ID Bernardi, Paolo (Author)
ID Pietrangelo, Laura (Author)
ID Boncompagni, Simona (Author)
ID Protasi, Feliciano (Author)
ID Paolocci, Nazareno (Author)
ID Reggiani, Carlo (Author) |
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| Files: |  URL - Source URL, visit https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14208
URL - Source URL, visit https://doi.org/10.1111/apha.14208
 PDF - Presentation file, download (3,97 MB)
MD5: 444CDA853D07DE6199EF14F51714D3ED
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  ZRS Koper - Science and Research Centre Koper
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| Abstract: | 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. |
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| Keywords: | calcium, mitochondria, mouse skeletal muscle fibers, parvalbumin, reaction-diffusion model |
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| Publication version: | Version of Record |
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| Submitted for review: | 09.07.2024 |
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| Article acceptance date: | 15.07.2024 |
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| Publication date: | 30.07.2024 |
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| Year of publishing: | 2024 |
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| Number of pages: | str. 1-14 |
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| Numbering: | Vol. 240, ǂiss.ǂ9 |
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| UDC: | 612 |
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| ISSN on article: | 1748-1716 |
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| DOI: | 10.1111/apha.14208  |
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| COBISS.SI-ID: | 214814467 |
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| Copyright: | © 2024 The Author(s) |
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| Note: | Opis vira z dne 13. 11. 2024;
Nasl. z nasl. zaslona;
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| Publication date in DiRROS: | 13.11.2024 |
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| Views: | 38 |
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| Downloads: | 16 |
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