American journal of physiology. Cell physiology最新文献

{"title":"Modeling statin-induced myopathy with hiPSC-derived myocytes reveals that impaired proteostasis underlies the myotoxicity and is targetable for the prevention.","authors":"Xiaolin Zhao, Liyang Ni, Miharu Kubo, Mariko Matsuto, Hidetoshi Sakurai, Makoto Shimizu, Yu Takahashi, Ryuichiro Sato, Yoshio Yamauchi","doi":"10.1152/ajpcell.00714.2024","DOIUrl":"10.1152/ajpcell.00714.2024","url":null,"abstract":"<p><p>Statins, 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors, have been widely prescribed to lower circulating low-density lipoprotein cholesterol levels and reduce the risk of cardiovascular disease. Although statins are well tolerated, statin-associated muscle symptoms (SAMS) are the major adverse effect and cause statin intolerance. Therefore, understanding the molecular mechanisms of SAMS and developing effective strategies for its prevention are of significant clinical importance; however, both remain unclear. Here, we establish a model of statin-induced myopathy (SIM) with human induced pluripotent stem cell (hiPSC)-derived myocytes (iPSC-MCs) and investigate the effect of statins on protein homeostasis (proteostasis) that affects skeletal muscle wasting and myotoxicity. We show that treating hiPSC-MCs with statins induces atrophic phenotype and myotoxicity, establishing an hiPSC-based SIM model. We then examine whether statins impair the balance between protein synthesis and degradation. The results show that statins not only suppress protein synthesis but also promote protein degradation by upregulating the expression of the muscle-specific E3 ubiquitin ligase Atrogin-1 in a mevalonate pathway-dependent manner. Mechanistically, blocking the mevalonate pathway inactivates the protein kinase Akt, leading to the inhibition of mTOR complex 1 (mTORC1) but the activation of GSK3β and FOXO1. These changes explain the statin-induced impairment in proteostasis. Finally, we show that pharmacological blockage of FOXO1 prevents SIM in hiPSC-MCs, implicating FOXO1 as a key mediator of SIM. Taken together, this study suggests that the mevalonate pathway is critical for maintaining skeletal muscle proteostasis and identifies FOXO1 as a potential target for preventing SIM.<b>NEW & NOTEWORTHY</b> This work established a human induced pluripotent stem (iPS) cell-based model for statin-induced myopathy (SIM) and demonstrated that blocking the mevalonate pathway disrupts the balance between protein synthesis and degradation, leading to myopathy. Furthermore, the present study showed that pharmacological inhibition of the transcription factor FOXO1 prevents SIM in human iPS cell-derived myocytes, suggesting that FOXO1 is a key mediator of SIM and a potential target for its prevention.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1247-C1259"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utilizing ¹³C-Labeled internal standards to advance the analysis of heparan sulfate.","authors":"Zhangjie Wang, Jian Liu","doi":"10.1152/ajpcell.00944.2024","DOIUrl":"10.1152/ajpcell.00944.2024","url":null,"abstract":"<p><p>Heparan sulfate (HS) is a highly sulfated and structurally heterogeneous polysaccharide that plays key roles in numerous biological processes. Due to its complex structure and variable sulfation patterns, accurately characterizing and quantifying HS in biological samples poses significant analytical challenges. This review presents an advanced high-performance liquid chromatography-tandem mass spectroscopy (LC-MS/MS) methodology that utilizes isotope-labeled internal standards for the precise quantification of HS disaccharides and rare 3-<i>O</i>-sulfated tetrasaccharides, alongside monitoring 6-<i>O</i>-endosulfatase enzyme activity and the metabolism of synthetic HS oligosaccharides in biological systems. The combination of isotope-labeled standards with LC-MS/MS technology provides a powerful and sensitive approach for comprehensive analysis of HS modifications, offering valuable insights into HS metabolism and its alterations across various biological contexts.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1091-C1100"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GSK3 inhibition ameliorates the abnormal contractility of Newfoundland ACM patient iPSC-cardiomyocytes.","authors":"Rebecca J Noort, Wesam Salman, Camila Fuchs, Ursula Braun, David Pace, Kathleen A Hodgkinson, Jessica L Esseltine","doi":"10.1152/ajpcell.01025.2024","DOIUrl":"10.1152/ajpcell.01025.2024","url":null,"abstract":"<p><p>Arrhythmogenic cardiomyopathy (ACM) is clinically characterized by ventricular arrhythmias causing sudden cardiac death and fibrofatty replacement of the myocardium, leading to heart failure. One form of ACM is highly prevalent in the Canadian Province of Newfoundland and Labrador (NL) and has earned the moniker, \"The Newfoundland Curse\". ACM in NL is often caused by a fully penetrant heterozygous missense pathogenic variant in the <i>TMEM43</i> gene (<i>TMEM43</i> c.1073C>T; TMEM43 p.S358L). Although the causative variant has been identified, little is known about the function of the TMEM43 protein in cardiomyocytes, how the TMEM43 p.S358L mutation contributes to the development of arrhythmias, or why the disease is more severe in males than in females. To explore the role of TMEM43 in cardiomyocyte function, we generated induced pluripotent stem cells (iPSCs) from two severely affected male Newfoundland patients with ACM (TMEM43 p.S358L). CRISPR-Cas9 was used to genetically \"repair\" the heterozygous TMEM43 variant in ACM patient iPSCs. ACM patient iPSC-cardiomyocytes (iPSC-CMs) with the TMEM43 p.S358L variant display pro-arrhythmogenic phenotypes in vitro with significantly elevated contraction rates and altered calcium handling, although no obvious gross abnormalities were observed across several major intracellular organelles. GSK3 inhibition significantly increased the protein expression of β-catenin as well as Lamin A/C and ameliorated the proarrhythmic tendencies of ACM patient iPSC-CMs.<b>NEW & NOTEWORTHY</b> This is the first characterization of induced pluripotent stem cell-cardiomyocytes (iPSC-CMs) from Newfoundland patients with ACM. We find that ACM iPSC-CMs exhibit extreme proarrhythmic tendencies that can be normalized with GSK3 inhibition. Importantly, GSK3 inhibition is accompanied by a significant increase in key proteins, such as β-catenin and Lamin A/C, pointing toward a possible mechanism both for disease pathogenesis and therapy via GSK3 inhibitors.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1206-C1219"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic insights into SENP1 and OCT4 interaction in promoting drug resistance and stem cell features in colon cancer.","authors":"Jun Zou, Jing Chen, Lei Deng, Bangran Xu, Tenghua Yu, Jun Wang, Chongwu He","doi":"10.1152/ajpcell.00817.2024","DOIUrl":"10.1152/ajpcell.00817.2024","url":null,"abstract":"<p><p>This study explores the molecular mechanism by which sentrin/SUMO-specific protease 1 (SENP1) promotes cisplatin (Cis) resistance and tumor stem cell characteristics in colon adenocarcinoma (COAD) through deSUMOylation-mediated modification of octamer-binding transcription factor 4 (OCT4). By analyzing single-cell and transcriptome sequencing datasets, we identified key genes and regulatory pathways in both resistant and sensitive COAD cells. Malignant cells were isolated and evaluated for stemness using the infercnv package, and differential genes between Cis-resistant and -sensitive groups were identified. Machine learning algorithms highlighted essential genes, and databases predicted interaction sites between OCT4 and SENP1. In vitro experiments using enriched HCT116 stem cells revealed that SENP1 and OCT4 expression significantly elevated CD44 and CD133 levels, enhancing stemness. Functional assays showed that SENP1's deSUMOylation of OCT4 intensified Cis resistance, migration, and invasion in cisplatin-resistant cell line 116 (Cis-116) cells. In vivo, SENP1 knockdown reduced tumor growth and stem cell markers, whereas OCT4 overexpression escalated tumor metastasis and structural damage. These findings demonstrate that SENP1's modulation of OCT4 is central to COAD's resistance and stem cell properties, offering a novel target for COAD therapy.<b>NEW & NOTEWORTHY</b> This study uncovers the critical role of SENP1 in regulating OCT4 through deSUMOylation, driving Cis resistance and tumor stemness in COAD. Targeting this pathway may provide novel therapeutic strategies for COAD management.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1260-C1278"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in Synthetic Notch Receptors for Biomedical Application.","authors":"Luyao Song, Qinmeng Zhang, Hairu Sui, Chenlu Gao, Zhiwei Jiang","doi":"10.1152/ajpcell.00659.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00659.2024","url":null,"abstract":"<p><p>The synthetic Notch receptor has emerged as a potent tool for precisely modulating cellular functions. It constitutes a receptor system rooted in the Notch signaling pathway. SynNotch receptors, coupled with downstream transcription programs, hold promise for organoid and 3D tissue construction. Additionally, it enables the tracking and visualization of intercellular communication. Moreover, engineering SynNotch cells to carry specific receptors markedly enhances the efficacy and safety of immunotherapy. This review delineates the subdomains and tunable mechanisms of SynNotch, summarizing four core modes of combinatorial multiplexing potentially pivotal for regulating SynNotch cell functions. Furthermore, this review summarizes the multifaceted applications, advantages, and limitations of SynNotch, offering fresh insights into its future biomedical utilization.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The molecular circadian clock of eosinophils: A potential therapeutic target for asthma.","authors":"Julia Teppan, Thomas Bärnthaler, Aitak Farzi, Hannah Durrington, Gael Gioan-Tavernier, Hazel Platt, Peter Wolf, Akos Heinemann, Eva Maria Böhm","doi":"10.1152/ajpcell.00149.2025","DOIUrl":"https://doi.org/10.1152/ajpcell.00149.2025","url":null,"abstract":"<p><p>Asthma is a chronic inflammatory airway disease exhibiting time-of-day variability in symptoms and severity. Eosinophils, pivotal players and biomarkers in asthma, are regulated by the molecular circadian clock. This study aimed to investigate the impact of the molecular circadian clock on eosinophil effector function and its potential as a diagnostic biomarker and therapeutic target. We monitored clock proteins by flow cytometry in peripheral blood eosinophils from mild asthmatics over a 24-hour period. The observed decreased protein levels were confirmed in a cohort of patients with moderate asthma. To assess the interaction between inflammation and the molecular circadian clock, eosinophils were stimulated with patients' sera, inflammatory mediators, and clock-modulating ligands. The therapeutic potential of the inverse ROR agonist SR1001 was evaluated in vitro and in a murine model of allergen-induced airway inflammation. Altered protein levels of CLOCK, BMAL1, REV-ERBs, and RORs in eosinophils from asthmatics reflected the disease severity and allergy status of the patients. Mimicking an inflammatory environment in vitro resulted in similar changes. Blocking CCR3/ERK and EGFR signaling with an inverse ROR agonist SR1001 reset the molecular circadian clock in eosinophils and exhibited anti inflammatory effects by inhibiting eosinophil migration in vitro. Additionally, we confirmed the therapeutic potential of the clock-modulating SR1001, bronchoprotective effects in two in vivo models. This study suggests that clock proteins could serve as therapeutic targets in asthma. Pharmacological inhibition of ROR signaling demonstrated significant anti-inflammatory and bronchoprotective properties, indicating its potential as a novel treatment strategy for asthma and other eosinophilic diseases.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential of synergist ablation to study mechanisms of skeletal muscle hypertrophy in rodent disease models.","authors":"Fabio Sarto, Christopher S Fry, Marco V Narici, Lee Rubin, Feodor D Price","doi":"10.1152/ajpcell.00076.2025","DOIUrl":"https://doi.org/10.1152/ajpcell.00076.2025","url":null,"abstract":"<p><p>Synergist ablation (SA) is a well-established model of mechanical overload-induced hypertrophy in rodents, commonly used to infer skeletal muscle adaptation to resistance training in humans. Given the critical role of skeletal muscle atrophy in chronic conditions such as neuromuscular, metabolic, and cardiopulmonary disorders, SA represents a promising preclinical tool to study muscle hypertrophy mechanisms in pathological states. However, while extensively characterized in healthy animals, the potential applications of SA in disease models remain largely overlooked. This Mini-Review summarizes existing studies employing SA in rodent disease models, highlighting the diverse hypertrophic responses observed across conditions, including Duchenne muscular dystrophy, obesity, diabetes, cancer cachexia, and chronic kidney disease. Although hypertrophy gains are generally attenuated in diseased animals compared to healthy controls, SA-induced overload provides valuable insights into disease-specific regulatory mechanisms, including alterations in intracellular signaling, fiber-type transitions, and disease phenotype. We also discuss the strengths and limitations of SA as a preclinical model for resistance training in disease contexts and propose its broader adoption for mechanistic investigations into skeletal muscle plasticity under pathological conditions.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel lncRNA ABCE1-5 regulates pulmonary fibrosis by targeting KRT14.","authors":"Shuwei Gao, Yanqiu Wei, Chen Li, Bingbing Xie, Xinran Zhang, Ye Cui, Huaping Dai","doi":"10.1152/ajpcell.00374.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00374.2024","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a progressive and degenerative interstitial lung disease characterized by complex etiology, unclear pathogenesis, and high mortality. Long non-coding RNAs (lncRNAs) have been identified as key regulators in modulating the initiation, maintenance, and progression of pulmonary fibrosis. However, the precise pathological mechanisms through which lncRNAs are involved in IPF remain limited and require further elucidation. A novel lncABCE1-5 was identified as significantly decreased by an ncRNA microarray analysis in our eight IPF lung samples compared with three donor tissues and validated by qRT-PCR analysis in clinical lung samples. To investigate the biological function of ABCE1-5, we performed loss-and gain-of-function experiments in vitro and in vivo. LncABCE1-5 silencing promoted A549 cell migration and A549 and BEAS-2B cell apoptosis, while enhancing the expression of proteins associated with extracellular matrix deposition, whereas overexpression of ABCE1-5 partially attenuated TGF-β-induced fibrogenesis. Forced ABCE1-5 expression by intratracheal injection of adeno-associated virus 6 (AAV6) revealing the anti-fibrotic effect of ABCE1-5 in BLM-treated mice. Mechanistically, RNA pull-down-mass spectrometry and RIP assay demonstrated that ABCE1-5 directly binds to keratin14 (krt14) sequences, potentially impeding its expression by perturbing mRNA stability. Furthermore, decreased ABCE1-5 levels can promote krt14 expression and enhance the phosphorylation of both mTOR and Akt; overexpression of ABCE1-5 in BLM mouse lung tissue significantly attenuated the elevated levels of p-mTOR and p-AKT. Knockdown of krt14 reversed the activation of mTOR signaling mediated by ABCE1-5 silencing. Collectively, the downregulation of ABCE1-5 mediated krt14 activation, thereby activating mTOR/AKT signaling, to facilitate pulmonary fibrosis progression in IPF.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of High-Salt Intake on Glucose Metabolism, Liver Function, and the Microbiome in Rats: Influence of ACE Inhibitors and Angiotensin II Receptor Blockers.","authors":"Xiaoli Zhang, Mohamed M S Gaballa, Ahmed A Hasan, Yvonne Liu, Johann-Georg Hocher, Xin Chen, Liping Liu, Jian Li, Dominik Wigger, Christoph Reichetzeder, Saban Elitok, Burkhard Kleuser, Bernhard K Krämer, Berthold Hocher","doi":"10.1152/ajpcell.01036.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.01036.2024","url":null,"abstract":"<p><p><b>Abstract</b> <b>Background:</b> High-salt diets (HSD) are known to impact blood pressure and cardiovascular health, but their effects on glucose metabolism, liver function, and gut microbiota remain poorly understood. This study investigates how long-term HSD affects these physiological processes and evaluates the potential therapeutic effects of ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs). <b>Methods:</b> Male Sprague-Dawley rats were fed a normal salt diet (0.3% NaCl), a moderate salt diet (2% NaCl), or a high-salt diet (8% NaCl) for 12 weeks. Two subgroups in the HSD condition received telmisartan or enalapril. We assessed blood pressure, glucose homeostasis, liver inflammation, pancreatic function, and gut microbiota composition. <b>Results:</b> HSD rats exhibited significantly higher blood pressure (130 ± 2 mmHg in ND vs. 144 ± 4 mmHg in HSD; p < 0.01), reduced fasting insulin (1.33 ± 0.14 ng/mL in ND vs. 0.60 ± 0.05 ng/mL in HSD; p < 0.01), and gut microbiota dysbiosis, with a 71% reduction in Ruminococcus species (p = 0.018). Liver inflammation, indicated by an increase in CD68+ macrophages, was also observed in the HSD group. Telmisartan treatment significantly reduced liver inflammation but did not fully restore metabolic homeostasis. <b>Conclusion:</b> HSD disrupts multiple physiological systems, including glucose metabolism and liver function, partly through gut microbiota alterations. ACEIs and ARBs provided partial protection, highlighting the need for multi-targeted interventions to mitigate high-salt diet effects.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased contact between lipid droplets and mitochondria in skeletal muscles of male elite endurance athletes.","authors":"Joachim Nielsen, Kristine Grøsfjeld Petersen, Martin Eisemann de Almeida, Sam O Shepherd, Britt Christensen, Maria Houborg Petersen, Kurt Højlund, Niels Ørtenblad, Kasper Degn Gejl","doi":"10.1152/ajpcell.00123.2025","DOIUrl":"https://doi.org/10.1152/ajpcell.00123.2025","url":null,"abstract":"<p><p>Endurance athletes exhibit higher skeletal muscle mitochondrial and lipid droplet (LD) content compared to recreationally active individuals, along with greater whole-body oxygen uptake and maximal fat oxidation rates. In this study, we investigated if these differences manifest in a greater LD-mitochondria contact and how this may relate to the organelles' size, shape, and numerical densities. We obtained skeletal muscle biopsies from 17 male elite triathletes and road cyclists and 7 recreationally active men. Using quantitative transmission electron microscopy, we found that the endurance athletes had 2-3-fold greater LD-mitochondria total contact length than the recreationally active individuals. This was related to higher numerical densities of both mitochondria (+30%) and LDs (+100%) in the intermyofibrillar space. Adding data from untrained individuals with equally high intermyofibrillar LD density as the endurance athletes revealed a 24% greater total LD-mitochondria contact length in the endurance athletes. We observed small trivial differences in shape of both organelles between populations. However, large mitochondrial profiles were more elongated and irregular in shape than small mitochondrial profiles, while large LD profiles were more circular and less irregular than small LD profiles. Within athletes, large intermyofibrillar LD profiles correlated (r=0.72) with a high fraction of PLIN5-positive LDs and their maximal fat oxidation rate was positively associated with an interaction between the profile size of both intermyofibrillar LDs and mitochondria. In conclusion, male endurance athletes have a greater LD-mitochondria contact than recreationally active and untrained individuals. This muscular phenotype is restricted to the intermyofibrillar space and to fibers rich in mitochondria.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}