Cellular and Molecular Life Sciences最新文献

{"title":"RNA binding protein Pumilio2 promotes chemoresistance of pancreatic cancer via focal adhesion pathway and interacting with transcription factor EGR1.","authors":"Zhao Bangbo, Qin Cheng, Li Zeru, Li Tianyu, Zhao Yutong, Wang Weibin, Zhao Yupei","doi":"10.1007/s00018-025-05599-8","DOIUrl":"10.1007/s00018-025-05599-8","url":null,"abstract":"<p><p>Pancreatic cancer (PCa) has insidious onset, high malignancy and poor prognosis. Gemcitabine (GEM) is one of the first-line chemotherapy drugs for PCa. However, GEM resistance has always been a bottleneck problem leading to recurrence and death of PCa patients. RNA-binding proteins (RBPs) are important proteins that regulate transportation, splicing, stability and translation of RNA. Abnormal expression of RBPs often lead to a series of abnormal accumulation or degradation of downstream RNA resulting in various diseases. In our study, we utilized RIP seq, RIP-qPCR, in vitro and in vivo experiments and found that pumilio2 (PUM2) was high expression in PCa, and promoted GEM resistance of PCa by regulating mRNA stability of integrin Alpha 3 (ITGA3) and other genes in focal adhesion pathway, and there was positive feedback regulation between PUM2 and transcription factor early growth response gene 1 (EGR1), that is PUM2 binding to 3'UTR region of EGR1 mRNA, and EGR1 binding to promoter region of PUM2 gene. The discovery of EGR1/PUM2/ITGA3 axis provided a solid experimental basis for the selection of chemotherapy regiments for PCa patients and exploration of combined regimens to reverse GEM resistance in the future.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"78"},"PeriodicalIF":6.2,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439933","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 immune sensitivity caused by DUSP11, an RNA 5'-end maturation phosphatase, is adjusted by a human non-coding RNA, nc886.","authors":"Jiyoung Joan Jang, Myung-Ju Lee, Myung-Shin Lee, Jinjong Myoung, Hwi-Ho Lee, Byung-Han Choi, Enkhjin Saruuldalai, Yuh-Seog Jung, Hyun-Sung Lee, Yeochan Kim, TaeJin Ahn, Jong-Lyul Park, Seon-Young Kim, Gaeul Park, Sang-Jae Park, Sung-Hoon Kim, Ji-Hoon Kim, Nayoung Han, Eun Jung Park, Dongmin Kang, In-Hoo Kim, Yeon-Su Lee, Yong Sun Lee","doi":"10.1007/s00018-025-05607-x","DOIUrl":"10.1007/s00018-025-05607-x","url":null,"abstract":"<p><p>All cellular transcripts initially have a tri-phosphate (PPP) group at the 5'-end, recognized as a pathogen-associated molecular pattern (PAMP) by a cell's innate immune system. The removal of 5'-PPP occurs to varying extents, causing immune imbalance. However, how cells manage this situation has not yet been documented. Among 5'-PPP removal mechanisms, recent attention has been towards an RNA phosphatase called Dual Specificity Phosphatase 11 (DUSP11), which acts preferentially on 5'-triphosphorylated (5'-PPP) RNAs transcribed by RNA polymerase III (Pol III) and converts them to a 5'-monophosphorylated (5'-P) form. Here we have elucidated that immune imbalance caused by variable DUSP11 expression in human is controlled by a Pol III-transcribed non-coding RNA (Pol III-ncRNA), nc886. DUSP11 depletion leads to the accumulation of 5'-PPP-Pol III-ncRNAs, making cells respond better to incoming PAMP. Distinctly from other Pol III-ncRNAs, DUSP11 depletion increases the expression of nc886 in a 5'-P form, which mitigates the sensitized immunity. nc886 expression is also increased by infection with Kaposi's sarcoma-associated herpesvirus (KSHV) that suppresses DUSP11, and, in turn, nc886 stimulates KSHV infectivity. DUSP11 levels in normal tissues are relatively constitutive in mice lacking nc886 but are variable in humans. This wide range of DUSP11 expression and the resultant immune imbalance is probably adjusted by nc886. In summary, our study of DUSP11 and nc886 has uncovered a novel mechanism by which human cells control immune sensitivity, which is intrinsically caused by cellular RNA metabolism, allowing different states of equilibrium between immune status and gene expression.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"77"},"PeriodicalIF":6.2,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11828774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413591","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":"Enhanced secretion of the amyotrophic lateral sclerosis ALS-associated misfolded TDP-43 mediated by the ER-ubiquitin specific peptidase USP19.","authors":"Flavien Picard, Takashi Nonaka, Edwige Belotti, Alexis Osseni, Elisabeth Errazuriz-Cerda, Coline Jost-Mousseau, Emilien Bernard, Agnès Conjard-Duplany, Delphine Bohl, Masato Hasegawa, Cédric Raoul, Thierry Galli, Laurent Schaeffer, Pascal Leblanc","doi":"10.1007/s00018-025-05589-w","DOIUrl":"10.1007/s00018-025-05589-w","url":null,"abstract":"<p><p>Proteinopathies, such as amyotrophic lateral sclerosis (ALS), are marked by the accumulation of misfolded proteins that disrupt cellular processes. Eukaryotic cells have developed protein quality control systems to eliminate these aberrant proteins, but these systems often fail to differentiate between normal and misfolded proteins. In ALS, pathological inclusions primarily composed of misfolded TDP-43 are a hallmark of the disease. Recently, a novel unconventional secretion process called misfolding-associated protein secretion (MAPS) has been discovered to selectively export misfolded proteins. USP19, an Endoplasmic Reticulum-associated ubiquitin peptidase, plays a crucial role in this process. In this study, we investigated the impact of ER-anchored USP19 on the secretion of misfolded TDP-43. Here we found that USP19 overexpression significantly promotes the secretion of soluble and aggregated misfolded TDP-43, requiring both ER anchoring and ubiquitin peptidase activity. Characterization of the cellular and molecular mechanisms involved in this process highlighted the importance of early autophagosomal and late endosomal/amphisomal compartments, while lysosomes did not play a key role. By using dominant-negative mutants and small interfering RNAs, we identified that USP19-mediated secretion of misfolded TDP-43 is modulated by key factors involved in cellular trafficking and secretion pathways, such as ATG7, the ESCRT-O HGS/HRS, the Rab GTPases RAB11A, RAB8A, and RAB27A, and the v-SNARE VAMP7. We also confirmed the crucial role of the DNAJC5/CSPα cochaperone. Overall, this study provides new insights into how cells manage the secretion of misfolded TDP-43 proteins and potentially opens new avenues for therapeutic interventions in ALS and related disorders.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"76"},"PeriodicalIF":6.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413588","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":"Antiviral strategies against influenza virus: an update on approved and innovative therapeutic approaches.","authors":"Anna Bonomini, Beatrice Mercorelli, Arianna Loregian","doi":"10.1007/s00018-025-05611-1","DOIUrl":"10.1007/s00018-025-05611-1","url":null,"abstract":"<p><p>Influenza viruses still represent a great concern for Public Health by causing yearly seasonal epidemics and occasionally worldwide pandemics. Moreover, spillover events at the animal-human interface are becoming more frequent nowadays, also involving animal species not previously found as reservoirs. To restrict the effects of influenza virus epidemics, especially in at-risk population, and to prepare a drug arsenal for possible future pandemics, researchers worldwide have been working on the development of antiviral strategies since the 80's of the last century. One of the main obstacles is the considerable genomic variability of influenza viruses, which constantly poses the issues of drug-resistance emergence and immune evasion. This review summarizes the approved therapeutics for clinical management of influenza, promising new anti-flu compounds and monoclonal antibodies currently undergoing clinical evaluation, and molecules with efficacy against influenza virus in preclinical studies. Moreover, we discuss some innovative anti-influenza therapeutic approaches such as combination therapies and targeted protein degradation. Given the limited number of drugs approved for influenza treatment, there is a still strong need for novel potent anti-influenza drugs endowed with a high barrier to drug resistance and broad-spectrum activity against influenza viruses of animal origin that may be responsible of future large outbreaks and pandemics.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"75"},"PeriodicalIF":6.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406044","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":"SLPI controls neutrophil migration abilities and impacts neutrophil skin infiltration in experimental psoriasis.","authors":"Patrycja Kwiecinska, Michal Santocki, Joanna Skrzeczynska-Moncznik, Ivan Sinkevich, Katarzyna Piwowarczyk, Pawel Majewski, Beata Grygier, Monika Majchrzak-Gorecka, Jaroslaw Czyz, Elzbieta Kolaczkowska, Joanna Cichy","doi":"10.1007/s00018-025-05606-y","DOIUrl":"10.1007/s00018-025-05606-y","url":null,"abstract":"<p><p>Skin infiltration by neutrophils is a hallmark of the chronic inflammatory skin disease psoriasis, yet the mechanisms underlying neutrophil recruitment and positioning in chronically inflamed skin remain poorly understood. In this study, we demonstrate the significant impact of a total genetic deficiency of secretory leukocyte protease inhibitor (SLPI) on neutrophil migration in mouse skin. Without SLPI, neutrophils displayed an unconventional migratory pattern, characterized by altered interactions with vessel walls and reduced efficiency in extravasating from blood vessels into skin tissue during the early stages of experimental psoriasis. This was associated with changes in tissue motility, positioning neutrophils farther from the skin entry vessels and closer to the skin surface. Neutrophil diapedesis was partially dependent on SLPI within the neutrophils themselves. The impact of SLPI on neutrophil movement was further supported by the increased migration of human neutrophils in the presence of neutrophil-penetrant recombinant SLPI. Additionally, our data suggest that neutrophils with varying capacities for vessel wall interaction are released from the bone marrow into circulation in an SLPI-dependent manner. These findings establish a role for SLPI in regulating the spatiotemporal infiltration of neutrophils into the skin in psoriasis, highlighting its relevance to psoriasis pathophysiology.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"74"},"PeriodicalIF":6.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381620","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":"Ketogenic diet induces an inflammatory reactive astrocytes phenotype reducing glioma growth.","authors":"Maria Rosito, Javeria Maqbool, Alice Reccagni, Micol Mangano, Tiziano D'Andrea, Arianna Rinaldi, Giovanna Peruzzi, Beatrice Silvestri, Alessandro Rosa, Flavia Trettel, Giuseppina D'Alessandro, Myriam Catalano, Sergio Fucile, Cristina Limatola","doi":"10.1007/s00018-025-05600-4","DOIUrl":"10.1007/s00018-025-05600-4","url":null,"abstract":"<p><p>The use of a ketogenic diet (KD) in glioma is currently tested as an adjuvant treatment in standard chemotherapy regimens. The metabolic shift induced by the KD leads to the generation of ketone bodies that can influence glioma cells and the surrounding microenvironment, but the mechanisms have not yet been fully elucidated. Here, we investigated the potential involvement of glial cells as mediators of the KD-induced effects on tumor growth and survival rate in glioma-bearing mice. Specifically, we describe that exposing glioma-bearing mice to a KD or to β-hydroxybutyrate (β-HB), one of the main KD metabolic products, reduced glioma growth in vivo, induced a pro-inflammatory phenotype in astrocytes and increased functional glutamate transporters. Moreover, we described increased intracellular basal Ca²⁺ levels in GL261 glioma cells treated with β-HB or co-cultured with astrocytes. These data suggest that pro-inflammatory astrocytes triggered by β-HB can be beneficial in counteracting glioma proliferation and neuronal excitotoxicity, thus protecting brain parenchyma.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"73"},"PeriodicalIF":6.2,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373898","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":"Charcot Marie Tooth disease pathology is associated with mitochondrial dysfunction and lower glutathione production.","authors":"Nafisa R Komilova, Plamena R Angelova, Elisa Cali, Annarita Scardamaglia, Ulugbek Z Mirkhodjaev, Henry Houlden, Noemi Esteras, Andrey Y Abramov","doi":"10.1007/s00018-025-05612-0","DOIUrl":"10.1007/s00018-025-05612-0","url":null,"abstract":"<p><p>Charcot Marie Tooth (CMT) or hereditary motor and sensory neuropathy is a heterogeneous neurological disorder leading to nerve damage and muscle weakness. Although multiple mutations associated with CMT were identified, the cellular and molecular mechanisms of this pathology are still unclear, although most of the subtype of this disease involve mitochondrial dysfunction and oxidative stress in the mechanism of pathology. Using patients' fibroblasts of autosomal recessive, predominantly demyelinating form of CMT-CMT4B3 subtype, we studied the effect of these mutations on mitochondrial metabolism and redox balance. We have found that CMT4B3-associated mutations decrease mitochondrial membrane potential and mitochondrial NADH redox index suggesting an increase rate of mitochondrial respiration in these cells. However, mitochondrial dysfunction had no profound effect on the overall levels of ATP and on the energy capacity of these cells. Although the rate of reactive oxygen species production in mitochondria and cytosol in fibroblasts with CMT4B3 pathology was not significantly higher than in control, the level of GSH was significantly lower. Lower level of glutathione was most likely induced by the lower level of NADPH production, which was used for a GSH cycling, however, expression levels and activity of the major NADPH producing enzyme Glucose-6-Phosphate Dehydrogenase (G6PDH) was not altered. Low level of GSH renders the fibroblast with CMT4B3 pathology more sensitive to oxidative stress and further treatment of cells with hydroperoxide increases CMT patients' fibroblast death rates compared to control. Thus, CMT4B3 pathology makes cells vulnerable to oxidative stress due to the lack of major endogenous antioxidant GSH.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"72"},"PeriodicalIF":6.2,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363788","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":"Measurement of serum 1,5-AG provides insights for diabetes management and the anti-viral immune response.","authors":"Marcus Tong Zhen Wei, Linda A Gallo, Katina D Hulme, Fawaz Alzaid, Jean-Baptiste Julla, Emily S Dorey, Gilles Morineau, Keng Yih Chew, Emma J Grant, Stephanie Gras, Helen L Barett, Jean-Pierre Riveline, Meagan Carney, Kirsty R Short","doi":"10.1007/s00018-024-05568-7","DOIUrl":"10.1007/s00018-024-05568-7","url":null,"abstract":"<p><strong>Background: </strong>Achieving an in-range glycated haemoglobin (HbA1c) is essential for managing diabetes mellitus (DM). However, this parameter provides an estimate of long-term blood glucose control rather than daily glycaemic variations. Glycaemic variability can be more predictive than HbA1c in terms of identifying those at risk for diabetes complications, including risk of severe respiratory virus infections and is usually measured via a continuous glucose monitor (CGM). For individuals for whom a CGM is not available, serum 1,5 anhydroglucitol (1,5-AG) level has shown potential as an alternative method for monitoring glycaemic variability. Despite this, at present 1,5-AG is not routinely used in the clinical assessment of DM. Here, we aim to determine whether assessing 1,5-AG, in addition to HbA1c, is of any potential clinical utility to the management of DM for patients.</p><p><strong>Methods: </strong>Using machine learning and data derived from 78 patients with type I DM (for whom CGM data is available) we show that the combination of 1,5-AG and HbA1c improves the prediction of a patient's glycemia risk index (GRI) compared to HbA1c alone.</p><p><strong>Results: </strong>The GRI is an essential tool in the management of DM as it reflects both clinical priorities and patient centred outcomes. The inclusion of 1,5-AG in this prediction was particularly important for individuals who had very high or very low GRI. Furthermore, in the context of glycaemic variability and susceptibility to severe respiratory virus infections, we show that reduced 1,5-AG in the plasma is associated with reduced ex vivo CD4 + T cell cytokine responses to influenza virus in individuals with a matched HbA1c.</p><p><strong>Conclusions: </strong>Taken together, these data argue for an increased monitoring of 1,5-AG in the clinic for individuals without a CGM to provide additional insights for diabetes management.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"71"},"PeriodicalIF":6.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11803061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254967","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":"Unveiling the native architecture of adult cardiac tissue using the 3D-NaissI method.","authors":"Nicolas Pataluch, Céline Guilbeau-Frugier, Véronique Pons, Amandine Wahart, Clément Karsenty, Jean-Michel Sénard, Céline Gales","doi":"10.1007/s00018-025-05595-y","DOIUrl":"10.1007/s00018-025-05595-y","url":null,"abstract":"<p><p>Accurately imaging adult cardiac tissue in its native state is essential for regenerative medicine and understanding heart disease. Current fluorescence methods encounter challenges with tissue fixation. Here, we introduce the 3D-NaissI (3D-Native Tissue Imaging) method, which enables rapid, cost-effective imaging of fresh cardiac tissue samples in their closest native state, and has been extended to other tissues. We validated the efficacy of 3D-NaissI in preserving cardiac tissue integrity using small biopsies under hypothermic conditions in phosphate-buffered saline, offering unparalleled resolution in confocal microscopy for imaging fluorescent small molecules and antibodies. Compared to conventional histology, 3D-NaissI preserves cardiac tissue architecture and native protein epitopes, facilitating the use of a wide range of commercial antibodies without unmasking strategies. We successfully identified specific cardiac protein expression patterns in cardiomyocytes (CMs) from rodents and humans, including for the first time ACE2 localization in the lateral membrane/T-Tubules and SGTL2 in the sarcoplasmic reticulum. These findings shed light on COVID-19-related cardiac complications and suggest novel explanations for therapeutic benefits of iSGLT2 in HFpEF patients. Additionally, we challenge the notion of \"connexin-43 lateralization\" in heart pathology, suggesting it may be an artifact of cardiac fixation, as 3D-NaissI clearly revealed native connexin-43 expression at the lateral membrane of healthy CMs. We also discovered previously undocumented periodic ring-like 3D structures formed by pericytes that cover the lateral surfaces of CMs. These structures, positive for laminin-2, delineate a specific spatial architecture of laminin-2 receptors on the CM surface, underscoring the pivotal role of pericytes in CM function. Lastly, 3D-NaissI facilitates the mapping of native human protein expression in fresh cardiac autopsies, offering insights into both pathological and non-pathological contexts. Therefore, 3D-NaissI provides unparalleled insights into native cardiac tissue biology and holds the promise of advancing our understanding of physiology and pathophysiology, surpassing standard histology in both resolution and accuracy.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"70"},"PeriodicalIF":6.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188411","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":"Dnajc5b contributes to male fertility by maintaining the mitochondrial functions and autophagic homeostasis during spermiogenesis.","authors":"Dake Chen, Shiqin Zhou, Jinhua Tang, Hao Xiong, Jialian Li, Fenge Li","doi":"10.1007/s00018-024-05552-1","DOIUrl":"10.1007/s00018-024-05552-1","url":null,"abstract":"<p><p>DnaJ heat shock protein family member C5 beta (DNAJC5B), also known as cysteine-string protein beta, exhibits a prominent expression in testicular tissue and plays an important role in acrosomal exocytosis in vitro. Nevertheless, the precise role and underlying mechanism of DNAJC5B in spermatogenesis and male fertility remain poorly understood. The meta-analysis of RNA-sequencing datasets from porcine and murine testes reveals that Dnajc5b could be a pivotal factor in spermatogenesis. This study illustrates that male fertility declines with an increased ratio of abnormal spermatozoa in germ-cell knockout Dnajc5b mice. DNAJC5B has been identified as a mitochondrial protein with high expression in spermatids. The absence of DNAJC5B induces a cascade of mitochondrial damages, including oxidative stress, mitochondrial stress in the testes, and lower mitochondrial membrane potential of spermatozoa. In vivo and in vitro evidence demonstrates that DNAJC5B mitigates excessive cellular autophagy and mitophagy via DNAJ domain under environmental stress conditions, such as starvation or exposure to mitochondrial uncouplers FCCP and CCCP. This study highlights the important role of DNAJC5B in safeguarding male fertility by preserving mitochondrial function and regulating autophagy during spermiogenesis.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"69"},"PeriodicalIF":6.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078745","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}