Frontiers in Cell and Developmental Biology最新文献

{"title":"Development of a transformer-based deep learning algorithm for diabetic peripheral neuropathy classification using corneal confocal microscopy images.","authors":"Wenqu Chen, Danling Liao, Yuyang Deng, Jianzhang Hu","doi":"10.3389/fcell.2024.1484329","DOIUrl":"10.3389/fcell.2024.1484329","url":null,"abstract":"<p><strong>Background: </strong>Diabetic peripheral neuropathy (DPN) is common and can go unnoticed until it is firmly developed. This study aims to establish a transformer-based deep learning algorithm (DLA) to classify corneal confocal microscopy (CCM) images, identifying DPN in diabetic patients.</p><p><strong>Methods: </strong>Our classification model differs from traditional convolutional neural networks (CNNs) using a Swin transformer network with a hierarchical architecture backbone. Participants included those with (DPN+, n = 57) or without (DPN-, n = 37) DPN as determined by the updated Toronto consensus criteria. The CCM image dataset (consisting of 570 DPN+ and 370 DPN- images, with five images selected from each participant's left and right eyes) was randomly divided into training, validation, and test subsets at a 7:1:2 ratio, considering individual participants. The effectiveness of the algorithm was assessed using diagnostic accuracy measures, such as sensitivity, specificity, and accuracy, in conjunction with Grad-CAM visualization techniques to interpret the model's decisions.</p><p><strong>Results: </strong>In the DPN + group (n = 12), the transformer model successfully predicted all participants, while in the DPN- group (n = 7), one participant was misclassified as DPN+, with an area under the curve (AUC) of 0.9405 (95% CI 0.8166, 1.0000). Among the DPN + images (n = 120), 117 were correctly classified, and among the DPN- images (n = 70), 49 were correctly classified, with an AUC of 0.8996 (95% CI 0.8502, 0.9491). For single-image predictions, the transformer model achieved a superior AUC relative to the ResNet50 model (0.8761, 95% CI 0.8155, 0.9366), the Inception_v3 model (0.8802, 95% CI 0.8231, 0.9374), and the DenseNet121 model (0.8965, 95% CI 0.8438, 0.9491).</p><p><strong>Conclusion: </strong>Transformer-based networks outperform CNN-based networks in rapid binary DPN classification. Transformer-based DLAs have clinical DPN screening potential.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1484329"},"PeriodicalIF":4.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PD-1 inhibitor sintilimab treated patients with metastatic triple-negative breast cancer.","authors":"Yan Jia, Jie Zhang, Yehui Shi, Guolei Dong, Xiaojing Guo, Zhongsheng Tong","doi":"10.3389/fcell.2024.1430310","DOIUrl":"10.3389/fcell.2024.1430310","url":null,"abstract":"<p><strong>Purpose: </strong>Triple-negative breast cancer (TNBC) is a highly challenging subtype due to a unique tumor microenvironment. Several evidence (IMpassion130 trial and KEYNOTE-355 trial) supported the therapeutic effect of the immune checkpoint inhibitor in TNBC. However, the efficacy and safety of the PD-1 inhibitor sintilimab in breast cancer (BC) has not been well-investigated. So the real-world data on sintilimab-treated patients with metastatic BC were collected and analyzed in this study.</p><p><strong>Methods: </strong>The patients were eligible according to the requirements included: ages between 18 years and 75 years; recurrent or metastatic TNBC; measurable disease based on RECIST v1.1; no limitation on the prior systemic treatments; and ECOG performance status of 0-1. Patients received sintilimab 200 mg intravenously every 3 weeks until unacceptable toxicity or disease progression.</p><p><strong>Results: </strong>From 1 June 2019 to 1 October 2022, 40 female patients (median age, 55.5 years) with metastatic TNBC (mTNBC) were enrolled into the study. The median prior lines of systemic therapy for mTNBC was three (range, 1-8), with 60% of cases receiving at least three lines of therapy for metastatic disease. The visceral or brain metastasis was detected in 40.4% or 9.6% of patients, respectively. The median duration of response was 2.8 months (range, 0.7-21.0), and the median number of sintilimab doses administered was 4 (range, 1-30). The ORR and DCR were 22.5% and 72.5%, separately. The median PFS was 3.5 months (range, 1.4-21.0), with a 6-month PFS rate of 15.0% (6/40). The median OS was 52.5 months (range, 9.0-247.0) as of data cut-off. Common adverse effects were acceptable, and fatigue, skin rash, and pruritus were the frequent toxicity observed. Two cases of grade 3 curable adverse events were considered to be treatment-related. PD-L1-positive tumor was found in 40% cases (4/10) of mTNBC. Although statistical difference was not reached, the trend was obvious. Patients with PD-L1-positive tumor gained better treatment response, while the TMB-high carrier received more benefits of PFS and OS.</p><p><strong>Conclusion: </strong>In our study, preliminary evidence provided the anticancer activity and acceptable adverse effects of sintilimab administered every 3 weeks to pretreated patients with mTNBC. Sintilimab showed its efficacy and safety of immunotherapy for patients with advanced TNBC.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1430310"},"PeriodicalIF":4.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Telocytes of the male reproductive system: dynamic tissue organizers.","authors":"Bruno D A Sanches, Lara C Rocha, J Pimentel Neto, Mateus Rodrigues Beguelini, Adriano P Ciena, Hernandes F Carvalho","doi":"10.3389/fcell.2024.1444156","DOIUrl":"10.3389/fcell.2024.1444156","url":null,"abstract":"<p><p>Telocytes are CD34⁺ interstitial cells that have long cytoplasmic projections (called telopodes), and have been detected in several organs, including those of the male reproductive system. In this brief review we evaluate the role of telocytes in tissue organization of the different organs of the male reproductive system in which these cells were studied. In general terms, telocytes act in the tissue organization through networks of telopodes that separate the epithelia from the stroma, as well as dividing the stroma into different compartments. In addition to this contribution to the structural integrity, there is direct and indirect evidence that such \"walls\" formed by telocytes also compartmentalize paracrine factors that they or other cells produce, which have a direct impact on morphogenesis and the maintenance of organ cell differentiation, as well as on their normal physiology. Moreover, alterations in telocytes and telopode networks are correlated with pathological conditions in the male reproductive system, in response to profound changes in structural organization of the organs, in inflammation, hyperplasia and cancer. Further studies are necessary to evaluate the molecular pathways telocytes employ in different contexts of physiology and disease.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1444156"},"PeriodicalIF":4.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polysaccharide-based hydrogels for cartilage regeneration.","authors":"Ning Chen, Sidi Li, Congrui Miao, Qin Zhao, Jinlei Dong, Lianxin Li, Ci Li","doi":"10.3389/fcell.2024.1444358","DOIUrl":"10.3389/fcell.2024.1444358","url":null,"abstract":"<p><p>Cartilage defect is one of the common tissue defect clinical diseases and may finally lead to osteoarthritis (OA) which threat patients' physical and psychological health. Polysaccharide is the main component of extracellular matrix (ECM) in cartilage tissue. In the past decades, polysaccharide-based hydrogels have shown great potential for cartilage regeneration considering unique qualities such as biocompatibility, enhanced cell proliferation, drug delivery, low toxicity, and many others. Structures such as chain length and chain branching make polysaccharides have different physical and chemical properties. In this review, cartilage diseases and current treatment options of polysaccharide-based hydrogels for cartilage defection repair were illustrated. We focus on how components and structures of recently developed materials affect the performance. The challenges and perspectives for polysaccharide-based hydrogels in cartilage repair and regeneration were also discussed in depth.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1444358"},"PeriodicalIF":4.6,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 dual role of autophagy in suppressing and promoting hepatocellular carcinoma.","authors":"Wasnaa H Mohammed, Ghassan M Sulaiman, Mosleh M Abomughaid, Daniel J Klionsky, Mohammed H Abu-Alghayth","doi":"10.3389/fcell.2024.1472574","DOIUrl":"10.3389/fcell.2024.1472574","url":null,"abstract":"<p><p>The 5-year survival rate for hepatocellular carcinoma (HCC), a deadly form of liver cancer, is quite low. Although drug therapy is successful, patients with advanced liver cancer frequently develop resistance because of the significant phenotypic and genetic heterogeneity of these cells. The overexpression of drug efflux transporters, downstream adaptive responses, malfunctioning DNA damage repair, epigenetic modification, the tumor microenvironment, and the extracellular matrix can all be linked to drug resistance. The evolutionary process of autophagy, which is in charge of intracellular breakdown, is intimately linked to medication resistance in HCC. Autophagy is involved in both the promotion and suppression of cancer by influencing treatment resistance, metastasis, carcinogenesis, and the viability of stem cells. Certain autophagy regulators are employed in anticancer treatment; however, because of the dual functions of autophagy, their use is restricted, and therapeutic failure is increased. By focusing on autophagy, it is possible to reduce HCC expansion and metastasis, and enhance tumor cell reactivity to treatment. Macroautophagy, the best-characterized type of autophagy, involves the formation of a sequestering compartment termed a phagophore, which surrounds and encloses aberrant or superfluous components. The phagophore matures into a double-membrane autophagosome that delivers the cargo to the lysosome; lysosomes and autophagosomes fuse to degrade and recycle the cargo. Macroautophagy plays dual functions in both promoting and suppressing cancer in a variety of cancer types.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1472574"},"PeriodicalIF":4.6,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-resolution visual Mamba with multi-directional selective mechanism for retinal disease detection.","authors":"Qiankun Zuo, Zhengkun Shi, Bo Liu, Na Ping, Jiangtao Wang, Xi Cheng, Kexin Zhang, Jia Guo, Yixian Wu, Jin Hong","doi":"10.3389/fcell.2024.1484880","DOIUrl":"10.3389/fcell.2024.1484880","url":null,"abstract":"<p><strong>Introduction: </strong>Retinal diseases significantly impact patients' quality of life and increase social medical costs. Optical coherence tomography (OCT) offers high-resolution imaging for precise detection and monitoring of these conditions. While deep learning techniques have been employed to extract features from OCT images for classification, convolutional neural networks (CNNs) often fail to capture global context due to their focus on local receptive fields. Transformer-based methods, on the other hand, suffer from quadratic complexity when handling long-range dependencies.</p><p><strong>Methods: </strong>To overcome these limitations, we introduce the Multi-Resolution Visual Mamba (MRVM) model, which addresses long-range dependencies with linear computational complexity for OCT image classification. The MRVM model initially employs convolution to extract local features and subsequently utilizes the retinal Mamba to capture global dependencies. By integrating multi-scale global features, the MRVM enhances classification accuracy and overall performance. Additionally, the multi-directional selection mechanism (MSM) within the retinal Mamba improves feature extraction by concentrating on various directions, thereby better capturing complex, orientation-specific retinal patterns.</p><p><strong>Results: </strong>Experimental results demonstrate that the MRVM model excels in differentiating retinal images with various lesions, achieving superior detection accuracy compared to traditional methods, with overall accuracies of 98.98% and 96.21% on two public datasets, respectively.</p><p><strong>Discussion: </strong>This approach offers a novel perspective for accurately identifying retinal diseases and could contribute to the development of more robust artificial intelligence algorithms and recognition systems for medical image-assisted diagnosis.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1484880"},"PeriodicalIF":4.6,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Notch signaling regulates pulmonary fibrosis.","authors":"Xinyue Zhang, Zhihao Xu, Qi Chen, Zhimin Zhou","doi":"10.3389/fcell.2024.1450038","DOIUrl":"https://doi.org/10.3389/fcell.2024.1450038","url":null,"abstract":"<p><p>Pulmonary fibrosis is a progressive interstitial lung disease associated with aging. The pathogenesis of pulmonary fibrosis remains unclear, however, alveolar epithelial cell injury, myofibroblast activation, and extracellular matrix (ECM) accumulation are recognized as key contributors. Moreover, recent studies have implicated cellular senescence, endothelial-mesenchymal transition (EndMT), and epigenetic modifications in the pathogenesis of fibrotic diseases. Various signaling pathways regulate pulmonary fibrosis, including the TGF-β, Notch, Wnt, Hedgehog, and mTOR pathways. Among these, the TGF-β pathway is extensively studied, while the Notch pathway has emerged as a recent research focus. The Notch pathway influences the fibrotic process by modulating immune cell differentiation (e.g., macrophages, lymphocytes), inhibiting autophagy, and promoting interstitial transformation. Consequently, inhibiting Notch signaling represents a promising approach to mitigating pulmonary fibrosis. In this review, we discuss the role of Notch signaling pathway in pulmonary fibrosis, aiming to offer insights for future therapeutic investigations.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1450038"},"PeriodicalIF":4.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142516363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kaempferol enhances intestinal repair and inhibits the hyperproliferation of aging intestinal stem cells in <i>Drosophila</i>.","authors":"Liusha Zhao, Ting Luo, Hong Zhang, Xinxin Fan, Qiaoqiao Zhang, Haiyang Chen","doi":"10.3389/fcell.2024.1491740","DOIUrl":"https://doi.org/10.3389/fcell.2024.1491740","url":null,"abstract":"<p><strong>Introduction: </strong>Intestinal stem cells (ISCs) are crucial for tissue repair and homeostasis because of their ability to self-renew and differentiate. However, their functionality declines significantly with age, resulting in reduced tissue regeneration and a higher risk of age-related diseases. Addressing this decline in ISC performance during aging presents a substantial challenge. The specific impact of nutrients or dietary elements on ISC adaptive resizing is urgent to explore.</p><p><strong>Methods: </strong><i>Drosophila</i> ISCs are an ideal model for studying development and aging because of their genetic richness, ease of manipulation, and similarity to mammalian tissues. As the primary mitotically active cells in the <i>Drosophila</i> gut, ISCs are flexible in response to dietary and stress signals. Manipulating signaling pathways or dietary restrictions has shown promise in regulating ISC functions and extending lifespan in flies, these approaches face broader applications for aging research.</p><p><strong>Results: </strong>Kaempferol is well-regarded for its antioxidant, anti-inflammatory, and potential anticancer effects. However, its impacts on ISCs and the associated mechanisms remain inadequately understood. Our findings indicate that Kaempferol accelerates gut recovery after damage and improves the organism's stress tolerance. Moreover, Kaempferol suppresses the hyperproliferation of aging ISCs in <i>Drosophila</i>. Further investigation revealed that the regulatory effects of Kaempferol on ISCs are mediated through the reduction of endoplasmic reticulum (ER) stress in aging flies and the modulation of excessive reactive oxygen species (ROS) levels via ER-stress pathways. Furthermore, Kaempferol exerts regulatory effects on the insulin signaling pathway, thereby contributing to the attenuation of ISC senescence.</p><p><strong>Discussion: </strong>This study reveals that Kaempferol promotes intestinal homeostasis and longevity in aging flies by targeting ER stress and insulin signaling pathways, though the exact molecular mechanisms require further exploration. Future research will aim to dissect the downstream signaling events involved in these pathways to better understand how Kaempferol exerts its protective effects at the molecular level.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1491740"},"PeriodicalIF":4.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DeepO-GlcNAc: a web server for prediction of protein O-GlcNAcylation sites using deep learning combined with attention mechanism.","authors":"Liyuan Zhang, Tingzhi Deng, Shuijing Pan, Minghui Zhang, Yusen Zhang, Chunhua Yang, Xiaoyong Yang, Geng Tian, Jia Mi","doi":"10.3389/fcell.2024.1456728","DOIUrl":"https://doi.org/10.3389/fcell.2024.1456728","url":null,"abstract":"<p><strong>Introduction: </strong>Protein O-GlcNAcylation is a dynamic post-translational modification involved in major cellular processes and associated with many human diseases. Bioinformatic prediction of O-GlcNAc sites before experimental validation is a challenge task in O-GlcNAc research. Recent advancements in deep learning algorithms and the availability of O-GlcNAc proteomics data present an opportunity to improve O-GlcNAc site prediction.</p><p><strong>Objectives: </strong>This study aims to develop a deep learning-based tool to improve O-GlcNAcylation site prediction.</p><p><strong>Methods: </strong>We construct an annotated unbalanced O-GlcNAcylation data set and propose a new deep learning framework, DeepO-GlcNAc, using Long Short-Term Memory (LSTM), Convolutional Neural Networks (CNN) combined with attention mechanism.</p><p><strong>Results: </strong>The ablation study confirms that the additional model components in DeepO-GlcNAc, such as attention mechanisms and LSTM, contribute positively to improving prediction performance. Our model demonstrates strong robustness across five cross-species datasets, excluding humans. We also compare our model with three external predictors using an independent dataset. Our results demonstrated that DeepO-GlcNAc outperforms the external predictors, achieving an accuracy of 92%, an average precision of 72%, a MCC of 0.60, and an AUC of 92% in ROC analysis. Moreover, we have implemented DeepO-GlcNAc as a web server to facilitate further investigation and usage by the scientific community.</p><p><strong>Conclusion: </strong>Our work demonstrates the feasibility of utilizing deep learning for O-GlcNAc site prediction and provides a novel tool for O-GlcNAc investigation.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1456728"},"PeriodicalIF":4.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple roles of mitochondrial autophagy receptor FUNDC1 in mitochondrial events and kidney disease.","authors":"Kaiqing Li, Xue Xia, Ying Tong","doi":"10.3389/fcell.2024.1453365","DOIUrl":"https://doi.org/10.3389/fcell.2024.1453365","url":null,"abstract":"<p><p>This article reviews the latest research progress on the role of mitochondrial autophagy receptor FUN14 domain containing 1 (FUNDC1) in mitochondrial events and kidney disease. FUNDC1 is a protein located in the outer membrane of mitochondria, which maintains the function and quality of mitochondria by regulating mitochondrial autophagy, that is, the selective degradation process of mitochondria. The structural characteristics of FUNDC1 enable it to respond to intracellular signal changes and regulate the activity of mitochondrial autophagy through phosphorylation and dephosphorylation. During phosphorylation, unc-51-like kinase 1 (ULK1) promotes the activation of mitophagy by phosphorylating Ser17 of FUNDC1. In contrast, Src and CK2 kinases inhibit the interaction between FUNDC1 and LC3 by phosphorylating Tyr18 and Ser13, thereby inhibiting mitophagy. During dephosphorylation, PGAM5 phosphatase enhances the interaction between FUNDC1 and LC3 by dephosphorylating Ser13, thereby activating mitophagy. BCL2L1 inhibits the activity of PGAM5 by interacting with PGAM5, thereby preventing the dephosphorylation of FUNDC1 and inhibiting mitophagy. FUNDC1 plays an important role in mitochondrial events, participating in mitochondrial fission, maintaining the homeostasis of iron and proteins in mitochondrial matrix, and mediating crosstalk between mitochondria, endoplasmic reticulum and lysosomes, which have important effects on cell energy metabolism and programmed death. In the aspect of kidney disease, the abnormal function of FUNDC1 is closely related to the occurrence and development of many diseases. In acute kidney injury (AKI), cardiorenal syndrome (CRS), diabetic nephropathy (DN), chronic kidney disease (CKD) ,renal fibrosis (RF) and renal anemia, FUNDC1-mediated imbalance of mitophagy may be one of the key factors in disease progression. Therefore, in-depth study of the regulatory mechanism and function of FUNDC1 is of great significance for understanding the pathogenesis of renal disease and developing new treatment strategies.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1453365"},"PeriodicalIF":4.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}