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Calcium Homeostasis of Cells in Health and Disease: Third Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 30 September 2025 | Viewed by 733

Special Issue Editors


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Guest Editor
Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98., H-4002 Debrecen, Hungary
Interests: skeletal muscle; intracellular calcium; excitation contraction coupling; muscle force; myopathies; aging; antioxidants
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Guest Editor
Department of Physiology, Medical Faculty, University of Debrecen, H-4002 Debrecen, Hungary
Interests: calcium signaling; skeletal muscle; excitation-contraction coupling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issue, “Calcium Homeostasis of Cells in Health and Disease: 2nd Edition”.

Whether in health or disease, calcium ions (Ca2+) play an important role in stimuli by responding to the processes of cells as a second messenger. In this process, the body maintains a low intracellular Ca2+ concentration at rest and mobilizes Ca2+ in response to stimuli, which activates cellular functions. This second-messenger role of Ca2+ was first discovered during the excitation–contraction coupling of skeletal muscle. Since then, the characteristics of Ca2+ as a second messenger (the variety of its targets, its ability to achieve quick and substantial transient and oscillatory mobilization, and its ability to cause localized and generalized cell responses) have been widely studied.

Although calcium has been extensively investigated in a variety of cells, many of its features are still uncertain; for example, what is its role in physiological and pathological circumstances? A few studies have shown that the Ca2+ homeostasis of cells changes during development and as they age. The latter is becoming increasingly important, as the Earth’s population is increasingly living longer. Thus, aging is a hot topic in research on humans. In addition, alterations in calcium homeostasis can occur in several diseases. New technological challenges and innovations in the use of calcium sensors have deepened our knowledge in this field, enabling us to study calcium concentrations outside and inside cells and even in cell organelles.

The aim of this Special Issue is to collect novel data regarding the role of calcium in the functioning of cells. We encourage the submission of manuscripts presenting innovative strategies to maintain and/or improve cell functions in aging and diseases.

Dr. Péter Szentesi
Prof. Dr. László Csernoch
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • Ca2+
  • calcium homeostasis
  • calcium-binding proteins
  • aging
  • disease

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Published Papers (2 papers)

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17 pages, 2994 KiB  
Article
Structural Insights and Calcium-Switching Mechanism of Fasciola hepatica Calcium-Binding Protein FhCaBP4
by Byeongmin Shin, Seonha Park, Ingyo Park, Hongchul Shin, Kyuhyeon Bang, Sulhee Kim and Kwang Yeon Hwang
Int. J. Mol. Sci. 2025, 26(15), 7584; https://doi.org/10.3390/ijms26157584 - 5 Aug 2025
Abstract
Fasciola hepatica remains a global health and economic concern, and treatment still relies heavily on triclabendazole. At the parasite–host interface, F. hepatica calcium-binding proteins (FhCaBPs) have a unique EF-hand/DLC-like domain fusion found only in trematodes. This makes it a parasite-specific target for small [...] Read more.
Fasciola hepatica remains a global health and economic concern, and treatment still relies heavily on triclabendazole. At the parasite–host interface, F. hepatica calcium-binding proteins (FhCaBPs) have a unique EF-hand/DLC-like domain fusion found only in trematodes. This makes it a parasite-specific target for small compounds and vaccinations. To enable novel therapeutic strategies, we report the first elevated-resolution structure of a full-length FhCaBP4. The apo structure was determined at 1.93 Å resolution, revealing a homodimer architecture that integrates an N-terminal, calmodulin-like, EF-hand pair with a C-terminal dynein light chain (DLC)-like domain. Structure-guided in silico mutagenesis identified a flexible, 16-residue β4–β5 loop (LTGSYWMKFSHEPFMS) with an FSHEPF core that demonstrates greater energetic variability than its FhCaBP2 counterpart, likely explaining the distinct ligand-binding profiles of these paralogs. Molecular dynamics simulations and AlphaFold3 modeling suggest that EF-hand 2 acts as the primary calcium-binding site, with calcium coordination inducing partial rigidification and modest expansion of the protein structure. Microscale thermophoresis confirmed calcium as the major ligand, while calmodulin antagonists bound with lower affinity and praziquantel demonstrated no interaction. Thermal shift assays revealed calcium-dependent stabilization and a merger of biphasic unfolding transitions. These results suggest that FhCaBP4 functions as a calcium-responsive signaling hub, with an allosterically coupled EF-hand–DLC interface that could serve as a structurally tractable platform for drug targeting in trematodes. Full article
(This article belongs to the Special Issue Calcium Homeostasis of Cells in Health and Disease: Third Edition)
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29 pages, 3549 KiB  
Article
Physiological Muscle Function Is Controlled by the Skeletal Endocannabinoid System in Murine Skeletal Muscles
by Nyamkhuu Ganbat, Zoltán Singlár, Péter Szentesi, Elena Lilliu, Zoltán Márton Kohler, László Juhász, Anikó Keller-Pintér, Xaver Koenig, Fabio Arturo Iannotti, László Csernoch and Mónika Sztretye
Int. J. Mol. Sci. 2025, 26(11), 5291; https://doi.org/10.3390/ijms26115291 - 30 May 2025
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Abstract
The endocannabinoid system (ECS) is known to regulate crucial bodily functions, including healthy muscle activity. However, its precise roles in normal skeletal muscle function and the development of muscle disorders remain unclear. Previously, we developed a tamoxifen-inducible, skeletal muscle-specific CB1 receptor knockdown [...] Read more.
The endocannabinoid system (ECS) is known to regulate crucial bodily functions, including healthy muscle activity. However, its precise roles in normal skeletal muscle function and the development of muscle disorders remain unclear. Previously, we developed a tamoxifen-inducible, skeletal muscle-specific CB1 receptor knockdown (skmCB1-KD) mouse model using the Cre/LoxP system. In this study, we aimed to clarify the mechanisms behind the observed reduction in muscle force generation in these mice. To investigate this, we analyzed calcium dynamics following electrical stimulation-induced muscle fatigue, assessed store-operated calcium entry (SOCE), and performed functional analysis of mitochondrial respiration. Our findings suggest that the reduced muscle performance observed in vivo likely arises from interconnected alterations in ATP production by mitochondria. Moreover, in skmCB1-KD mice, we detected a significant decrease in a component of the respiratory chain (complex IV) and a slowed dissipation of mitochondrial membrane potential upon the addition of an un-coupler (FCCP). Full article
(This article belongs to the Special Issue Calcium Homeostasis of Cells in Health and Disease: Third Edition)
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