Journal of physiology and biochemistry最新文献

{"title":"Aryl hydrocarbon receptor deficiency leads to sex- and age-dependent colonic dysmotility in mice.","authors":"Alicia Valls, David Verdú, Sol Guerra-Ojeda, Teresa San-Miguel, Andrea Suarez, Javier Pereda, Verónica Gómez-Jiménez, José Viña, Maria D Mauricio, Eva Serna","doi":"10.1007/s13105-026-01208-9","DOIUrl":"10.1007/s13105-026-01208-9","url":null,"abstract":"<p><p>The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in xenobiotic sensing and multiple physiological functions, including intestinal homeostasis. Aging is associated with reduced colonic motility and constipation, but the contribution of AhR to intestinal motor function across sex and age remains incompletely defined. We performed a phenotypic characterization of AhR-deficient (AhR^-/-) and wild-type (WT) C57BL/6J mice in both sexes at two ages (young: 4-6 months; adult: 12-13 months). Lifespan, body weight, food and water intake were monitored longitudinally. Body composition (DXA), hematological parameters, fecal output features (number, length, moisture and stool color analysis), ex vivo colonic function in organ bath (spontaneous peristalsis with or without L-NAME and responses to acetylcholine and norepinephrine), histological muscle thickness, and molecular markers (PGP9.5 and NOS1 protein; Nos1, Nos2, Aqp1/3/4/8, Il6, Il10 gene expression) were assessed. AhR^-/- mice exhibited reduced survival and attenuated body weight gain, particularly in females, without differences in food consumption but with increased water intake. Fecal length and moisture were unchanged; however, AhR^-/- females displayed fewer stools at both ages. Ex vivo, spontaneous peristaltic amplitude was selectively reduced in AhR^-/- females at both ages, whereas males were unaffected. L-NAME increased spontaneous peristalsis in WT males but not in AhR^-/- males, suggesting impaired nitrergic modulation in the absence of AhR. Acetylcholine-induced contraction was reduced in young AhR^-/- females but not in adults. Histology revealed reduced colonic muscle thickness in young AhR^-/- females only, accompanied by decreased PGP9.5 protein expression. Gene expression showed sex- and age-dependent changes in Nos1/Nos2, aquaporins, and inflammatory markers. AhR deficiency leads to a sex-dependent colonic motor phenotype predominantly affecting females, integrating functional impairment with early neuromuscular remodeling and altered neural markers. These findings support AhR as a regulator of intestinal motor function with potential relevance to age-related dysmotility.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13375827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of dietary modifications in reversing damage induced by high-fat diet in rats.","authors":"Manuel Jiménez-García, Maria Magdalena Quetglas-Llabrés, Susana Esteban-Valdés, Maria Del Mar Ribas-Taberner, Antoni Sureda Gomila, David Moranta Mesquida, Silvia Tejada-Gavela","doi":"10.1007/s13105-026-01205-y","DOIUrl":"10.1007/s13105-026-01205-y","url":null,"abstract":"<p><p>Excessive dietary fat intake is a major health concern, contributing to the increasing prevalence of Metabolic Dysfunction Associated with Fatty Liver Disease (MAFLD) worldwide; different prevalence between sexes has been postulated but it is not clear. This study evaluated the effects of a high-fat diet (HFD) in Wistar rats and the impact of a transition to standard or antioxidant-rich diets in the same animals, exploring differences between sexes. Female and male animals were maintained for 5 months: control (chow diet) and HFD groups throughout the study, and two intervention groups switched after 3 months from HFD to standard or antioxidant-rich diets. Body weight was monitored, hepatic lipid accumulation, plasma levels of glucose, advanced glycation end-products, interleukin-6, and polyphenolic content, and hepatic oxidative stress markers (catalase, superoxide dismutase, glutathione peroxidase, and malondialdehyde) were measured, along with gene expression related to inflammation and lipid metabolism. HFD significantly increased body weight (females: 123.9 ± 13.57 g; males: 163.1 ± 9.97 g) and hepatic lipid accumulation (female proportion: 9.4 ± 0.4; male proportion: 10.5 ± 0.2) compared with control group (females: 28.96 ± 3.95 g; males: 86.29 ± 3.79 g, p < 0.01; 0% lipid deposits for both sexes), with higher effect on body weight in females. Dietary intervention led to a significant reduction in both parameters and for both sexes. Biomarkers of oxidative stress, inflammation and gene expression analysis showed that dietary modification reversed HFD-induced adverse effects in these parameters, restoring levels comparable to controls; with more consistent effects in animals of both sexes that switched to an antioxidant-rich diet. Indeed, this antioxidant-rich diet group showed higher levels of plasma polyphenols (females: 6.28 ± 0.46 ng/L; males: 6.85 ± 0.49 ng/L, p < 0.001) and a better antioxidant and inflammatory gene expression profile even compared with the group that switched to a chow diet. Overall, dietary modification mitigates several adverse effects of HFD, with antioxidant-rich diets showing greater efficacy across multiple endpoints, with similar effects in both sexes.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13369766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148436883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipose-derived mesenchymal stem cells improved acute renal failure induced by ischemia-reperfusion injury: Focusing on toll-like receptor 4 activity and endoplasmic reticulum stress response.","authors":"Leila Hafazeh, Mehri Kadkhodaee, Behjat Seifi, Fariba Akhondzadeh, Fereshteh Azedi, Hamid Noori, Mahdi Hajiaqaei, Mina Ranjbaran","doi":"10.1007/s13105-026-01207-w","DOIUrl":"10.1007/s13105-026-01207-w","url":null,"abstract":"<p><p>This study evaluated the efficacy of adipose-derived mesenchymal stem cells (AD-MSCs) in reducing pathological alterations linked to acute kidney injury (AKI) caused by ischemia-reperfusion injury (IRI). In this study, 18 male rats were divided into three groups: Sham, IRI, and IRI + AD-MSC. IRI was induced by clamping the renal pedicles for 45 min, while the Sham group animals underwent the same surgical procedure without vascular clamping. In the IRI + AD-MSC groups, immediately after clamp removal, the animals received an intraperitoneal injection of 1 × 10⁶ AD-MSCs. To enable tracking, AD-MSCs were transfected with green fluorescent protein (GFP). The distribution of these labeled cells was examined at 24 and 48 h post-transplantation in three additional rats. Forty-eight hours after reperfusion, serum and kidney tissue samples were collected. The labeled AD-MSCs were more widely distributed in the injured kidney area of the IRI + AD-MSC group compared to the control group. In the group treated with AD-MSCs, there were notable reductions in serum blood urea nitrogen (BUN) and creatinine levels (P < 0.001), along with improvements in renal tissue damage and oxidative stress (P < 0.01). Additionally, the IRI + AD-MSC group showed significant decreases in toll-like receptor-4 (TLR4) protein levels (P < 0.01) and pro-inflammatory factors (P < 0.001), as well as reduced levels of endoplasmic reticulum (ER) stress proteins compared to the IRI group. This study suggested that AD-MSCs administration alleviates AKI, possibly by modulating TLR4 activity, decreasing inflammation, and reducing ER stress.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148421998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the role of CB2 receptor in beta-hydroxybutyrate mediated modulation of.","authors":"Monika Iešmantaitė, Liutauras Usonis, Kristupas Čeika, Egidijus Šimoliūnas, Mantas Liudvinaitis, Nerea Soto-Arroyo, Isabel Moreno-Indias, Francisco J Tinahones, Daiva Baltriukienė, Virginia Mela","doi":"10.1007/s13105-026-01206-x","DOIUrl":"10.1007/s13105-026-01206-x","url":null,"abstract":"<p><p>The cannabinoid receptor type 2 (CB2R), primarily expressed in microglia, the brain's resident immune cells, acts as a central regulator of neuroinflammatory responses. When CB2R is activated, it triggers anti-inflammatory signaling, making it a promising target for modulating microglial function in neuroinflammatory diseases. The ketone body, β-hydroxybutyrate (BHB), is gaining attention as a therapeutic agent for neurodegenerative disorders due to its ability to modulate neuroinflammation and preserve blood-brain barrier integrity. One mechanism by which BHB exerts anti-inflammatory effects is through regulation of microglial function; however, the precise mechanisms remain unclear. Since the role of BHB in this context is unexplored, we used two neuroinflammation models to test the hypothesis that CB2R-associated signaling contributes to the effects of BHB. In a mouse model of diet-induced obesity (DIO), characterized by chronic low-grade neuroinflammation, BHB treatment promoted ramified microglial morphology and enhanced debris clearance while sparing synaptic elements. These changes were accompanied by alterations in CB2R-related signaling markers and a slight increase in hydroxycarboxylic acid receptor 2 (HCA2), a known BHB target. When primary microglial cultures were challenged with lipopolysaccharide (LPS), BHB helped restore their function. However, that benefit disappeared when CB2R was pharmacologically blocked. Importantly, BHB increased the expression of arginase 1 (Arg1), a hallmark of anti-inflammatory responses, a change reversed by CB2R blockade. Moreover, BHB reduced NF-κB signaling, and CB2R inhibition attenuated this effect, suggesting that CB2R-associated signaling contributes to BHB's anti-inflammatory actions. Collectively, our findings demonstrate that BHB's anti-inflammatory effects are mediated, at least in part, through CB2R signaling, providing new insight into its therapeutic potential for neuroinflammation.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13350206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship between muscle FNDC5, FGF21 mRNA, miR-150 and bone loss after sciatic denervation.","authors":"Teresa Priego, Elena Nebot-Valenzuela, Álvaro Moreno-Rupérez, Miriam Granado, Daniel Jaque, Peter Pietschmann, Ana Isabel Martín, Asunción López-Calderón","doi":"10.1007/s13105-026-01203-0","DOIUrl":"10.1007/s13105-026-01203-0","url":null,"abstract":"<p><p>It has been proposed that muscle influences adjacent bones, but the mechanisms by which muscle regulates bone physiology are not fully understood. Sciatic denervation is an experimental model that induces both skeletal muscle atrophy and osteoporosis. Therefore, the aim of this study was to analyze, in this animal model, expression of myokines in the atrophic soleus and its possible effect on changes in tibia microarchitectural parameters in 9-12 weeks old male rats. For this purpose, soleus insulin-like growth factor-1 (IGF-1), interleukin-6 (IL-6), fibronectin type III domain-containing 5 (FNDC5), fibroblast growth factor 21 (FGF21) mRNA, and miR-150, were measured by real-time PCR and tibia microarchitecture was assessed 3, 7, and 14 days after sciatic denervation. Denervation induced soleus atrophy and decreased trabecular bone density, thickness, and number. In the atrophic soleus, there was an increase in IL-6, IGF-1, and FGF21 mRNA, with a decrease in FNDC5 mRNA and miR-150 levels. No correlation between soleus IL-6 or IGF-1 and trabecular bone parameters was found. However, FGF21 was negatively correlated with trabecular bone mineral content, whereas FNDC5 mRNA and miR-150 levels were positively correlated. These data suggest that modifications in FGF21, FNDC5, and miR-150 during muscle atrophy may mediate muscle-bone crosstalk and contribute to bone loss, while IL-6 and IGF-1 do not seem to play a predominant role.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The regulatory effects of extracellular vesicles derived from adipose stem cells on tumor biological activity.","authors":"Ziyue Qi, Xiaoyun Zhang, Mengyan Liu, Xin Li, Wenbo Wang, XiaoDong Cui","doi":"10.1007/s13105-026-01202-1","DOIUrl":"10.1007/s13105-026-01202-1","url":null,"abstract":"<p><p>The field of malignant tumor diagnosis and treatment urgently requires innovative research perspectives to overcome the existing limitations. Extracellular vesicles (EVs) are crucial mediators of intercellular communication, offering novel avenues for regulating tumors. Among these, extracellular vesicles derived from adipose-derived stem cells (ADSC-EVs) have garnered significant attention because of their exceptional stability, safety profile, and ease of storage and transportation. Here, we first elucidate the biological foundation of ADSC-EVs, delineating their biogenesis pathway characterized by the \"early endosome-multivesicular body-extracellular release\" process, and highlight the heterogeneity of their molecular cargo. This cargo includes 148 regulatory microRNAs (such as the let-7 family and miR-122), 1,466 functional proteins, and various lipid molecules, thereby underpinning its multifunctional regulatory potential. Mechanistically, the dual role of ADSC-EVs is emphasized: on one hand, they can activate signaling pathways, such as PI3K/AKT, or modulate metabolic reprogramming to promote tumor proliferation; on the other hand, they exert tumor-suppressive effects by delivering specific microRNAs (e.g., miR-503-3p) and remodeling the tumor immune microenvironment to influence tumor progression. From an application standpoint, the tripartite value of ADSC-EVs is underscored: serving as potential biomarkers to assist in tumor diagnosis and classification, enabling targeted delivery of anticancer agents following engineering modifications, and functioning as acellular tools that circumvent the risks associated with conventional stem cell therapies. In summary, this study constructed a comprehensive framework for the application of ADSC-EVs in tumor diagnosis and treatment, providing both theoretical and practical support for overcoming therapeutic bottlenecks and developing precision strategies.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3 suppresses pyroptosis in obstructive sleep apnea-associated hypertension via YTHDF2-mediated SOX4 mRNA degradation.","authors":"Wenjun Zhu, Yanyan Hou, Can Yang, Yaping Tian, Linna Cao, Wenjun Li, Liang Xie, Lirong He","doi":"10.1007/s13105-026-01200-3","DOIUrl":"10.1007/s13105-026-01200-3","url":null,"abstract":"<p><p>Obstructive sleep apnea (OSA) is frequently complicated by hypertension, with approximately 60% of patients exhibiting both conditions. However, the epigenetic mechanisms underlying this comorbidity remain largely unexplored. N6-methyladenosine (m6A), the most abundant internal RNA modification, has emerged as a critical regulator of cardiovascular pathology, yet its role in OSA-associated hypertension (OSA-HTN) is unknown. Here, we investigated the contribution of m6A RNA methylation to OSA-HTN pathogenesis. In a chronic intermittent hypoxia (CIH) mouse model and hypoxia-stimulated aortic vascular smooth muscle cells (AVSMCs), we observed marked inflammatory injury, pyroptosis, and decreased expression of methyltransferase-like 3 (METTL3) along with global m6A levels. Overexpression of METTL3 significantly attenuated hypoxia-induced pyroptosis and inflammation by downregulating SRY-box transcription factor 4 (SOX4), a pro-inflammatory transcription factor. Mechanistically, CIH suppressed YTH N6-methyladenosine RNA-binding protein 2 (YTHDF2), an m6A reader that directly binds SOX4 mRNA, while METTL3-mediated m6A modification enhanced YTHDF2-dependent SOX4 mRNA degradation. Knockdown of YTHDF2 abolished the suppressive effect of METTL3 on SOX4 stability, confirming a METTL3-m6A-YTHDF2 regulatory axis. This METTL3-dependent regulation of YTHDF2-SOX4 interaction and SOX4 mRNA decay was also validated in mouse aortic endothelial cells. Furthermore, in vivo silencing of SOX4 alleviated CIH-induced pyroptosis and inflammation in cardiac and aortic tissues. Notably, pharmacological activation of METTL3 or METTL3 overexpression similarly attenuated CIH-induced cardiac and aortic tissue injury in OSA-HTN mice. In conclusion, our findings identify a novel METTL3-YTHDF2-SOX4 axis that governs hypoxia-induced pyroptosis and inflammation, providing new mechanistic insights into the epigenetic regulation of OSA-HTN and highlighting potential therapeutic targets.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148361246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene arrangement within concatemeric constructs governs the functional divergence of human and rat ASIC3 concatemers.","authors":"Dmitry I Osmakov, Yuliya V Korolkova, Ekaterina E Maleeva, Yulia A Logashina, Elisaveta S Dubodel, Kseniya I Lubova, Sergey G Koshelev, Yaroslav A Andreev, Sergey A Kozlov","doi":"10.1007/s13105-026-01201-2","DOIUrl":"10.1007/s13105-026-01201-2","url":null,"abstract":"<p><p>Acid-sensing ion channels (ASICs) are proton-gated sodium channels encoded by four genes in mammals. The ASIC3 isoform is widely expressed and plays a critical role in pain signaling and inflammatory responses. Despite a high degree of sequence homology between rat and human ASIC3 orthologs, they exhibit pronounced functional differences. Notably, rat ASIC3 undergoes steady-state desensitization (SSD) at extracellular pH values of 7.1-7.0, whereas human ASIC3 is largely desensitized at physiological pH (7.4-7.3), underscoring substantial interspecies divergence with important translational implications. In this study, we systematically investigated the functional properties of rat and human ASIC3 channels using concatemeric constructs that enable precise control over subunit stoichiometry and gene order within engineered trimeric assemblies. Using whole-cell electrophysiology, we show that homomeric concatemeric channels (r-r-r and h-h-h) closely recapitulate the biophysical properties of their respective wild-type channels. Substitution of a single subunit at the N-terminal position of the concatemer with an ASIC3 ortholog produced minimal functional perturbations and yielded channel properties most similar to those of the corresponding homomeric channel. In contrast, replacement of the C-terminal subunit resulted in the most pronounced shifts in pH₅₀SSD values and significant alterations in activation kinetics and current characteristics, indicating that functional properties of ASIC3 concatemers are strongly influenced by subunit position within the construct. Together, these findings demonstrate that both subunit composition and positional arrangement contribute to the functional behavior of engineered ASIC3 concatemers and provide a useful experimental framework for analyzing interspecies differences between rat and human ASIC3 channels. The results also highlight important limitations of concatemeric approaches, including the potential emergence of non-native channel properties in certain construct configurations.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148352212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria-sarcoplasmic reticulum crosstalk as a modulator of skeletal muscle mass.","authors":"Rafael A Casuso","doi":"10.1007/s13105-026-01198-8","DOIUrl":"10.1007/s13105-026-01198-8","url":null,"abstract":"<p><p>Preservation of skeletal muscle mass and function is a key feature of healthy ageing and relies on the tight coordination between protein synthesis and breakdown to maintain proteostatic balance. These processes impose a substantial energetic demand, highlighting the importance of mitochondrial function in skeletal muscle homeostasis. Increasing evidence indicates that mitochondria and the sarcoplasmic reticulum are functionally interconnected. Effective crosstalk between these organelles contributes to the integration of bioenergetic supply, Ca²⁺ handling, and proteostasis. Disruption of this communication network may impair adaptive stress responses, compromise protein quality control, and favour the development of anabolic resistance during ageing. This review synthesizes current evidence on mitochondria-sarcoplasmic reticulum communication. It further discusses how disruption of this crosstalk may promote anabolic resistance and skeletal muscle atrophy, with particular emphasis on its implications for age-related muscle decline.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13319665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148352268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The two faces of mitochondrial Ca²⁺ dysregulation in skeletal muscle: overload and deficiency.","authors":"Mikhail V Dubinin, Konstantin N Belosludtsev","doi":"10.1007/s13105-026-01197-9","DOIUrl":"10.1007/s13105-026-01197-9","url":null,"abstract":"<p><p>Mitochondrial Ca²⁺ dysregulation is a central pathogenic event in skeletal muscle disorders, yet the dichotomy between overload and deficiency is often overlooked. This review summarizes mechanisms governing mitochondrial Ca²⁺ transport and sarcoplasmic reticulum-mitochondria communication. We examine prerequisites of Ca²⁺ overload, including RyR1/SERCA dysfunction and mitochondrial calcium uniporter (MCU) complex remodeling, leading to suppressed ATP synthesis, reactive oxygen species overproduction, and necrosis. Conversely, we address mitochondrial Ca²⁺ deficiency in aging, sarcopenia, and diabetes, resulting from altered MCU stoichiometry and reduced organelle tethering, causing metabolic inflexibility and impaired antioxidant defense. Additionally, therapeutic strategies limiting Ca²⁺ overload and prospects of pharmacological MCU activation to enhance bioenergetics in sarcopenia are discussed.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148302200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}