Journal of Molecular Cell Biology最新文献_第2页

ALKBH3 is an NPM1-dependent nucleolar protein required for rRNA biogenesis and translation. ALKBH3是一种依赖npm1的核仁蛋白，是rRNA生物发生和翻译所必需的。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-08-17 DOI: 10.1093/jmcb/mjag030

Xixi Ma, Yuliang Huang, Hao Jin, Rui Zhang, Fangzhou Liu, Aifu Lin, Tianhua Zhou, Shanshan Xie

引用次数: 0

LPA deficiency in follicular fluid linked to impaired oocyte maturation through BCAA metabolism-mediated mitochondrial dysfunction. 卵泡液LPA缺乏通过BCAA代谢介导的线粒体功能障碍与卵母细胞成熟受损有关。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-08-13 DOI: 10.1093/jmcb/mjag028

Huanyu Yan, Jihong Yang, Chuchu Hong, Yangbai Li, Fei Mao, Xi Wang, Yun Qian

{"title":"LPA deficiency in follicular fluid linked to impaired oocyte maturation through BCAA metabolism-mediated mitochondrial dysfunction.","authors":"Huanyu Yan, Jihong Yang, Chuchu Hong, Yangbai Li, Fei Mao, Xi Wang, Yun Qian","doi":"10.1093/jmcb/mjag028","DOIUrl":"10.1093/jmcb/mjag028","url":null,"abstract":"Lysophosphatidic acid (LPA) is known to be crucial for oocyte developmental competence, but the underlying molecular mechanisms remain unclear. In this study, we investigated the mechanistic relationship between follicular fluid LPA levels and oocyte quality determinants using a cohort of assisted reproductive technology patients, correlating LPA abundance with follicle sensitivity indices. Transcriptome sequencing and metabolic flux analyses compared low versus high LPA groups. Functional validation employed gabapentin-mediated inhibition of branched-chain amino acid (BCAA) catabolism in oocytes, assessing meiotic maturation, mitochondrial function, and oxidative stress. We found that reduced LPA levels were associated with significant suppression of BCAA catabolic pathways, leading to accumulation of valine and leucine. Gabapentin inhibition of BCAA oxidation recapitulated the low-LPA phenotype, inducing severe meiotic defects characterized by aberrant spindle assembly, chromosomal misalignment, and pronounced DNA damage. These oocytes also exhibited mitochondrial dysfunction with disrupted organellar distribution and severely compromised membrane polarization, along with elevated reactive oxygen species. Our findings indicate that impaired BCAA metabolism under low-LPA conditions compromises oocyte quality through mitochondrial dysfunction and oxidative stress, suggesting LPA as a potential modulator of metabolic pathways during oocyte maturation and also suggesting novel therapeutic targets for improving assisted reproduction outcomes.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148722668","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}

引用次数: 0

Deciphering cell state transitions by logical modeling with single-cell transcriptome data. 通过单细胞转录组数据的逻辑建模来破译细胞状态转换。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-08-12 DOI: 10.1093/jmcb/mjag027

Namhee Kim, Kwang-Hyun Cho

引用次数: 0

Loss of the cardiac-enriched mitochondrial transporter SLC25A34 promotes heart failure by attenuating fatty acid oxidation. 心肌富集线粒体转运体SLC25A34的缺失通过减弱脂肪酸氧化促进心力衰竭。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-08-10 DOI: 10.1093/jmcb/mjag026

Jieyuan Xue, Yin Long, Jiayu Zhou, Yuxuan Chen, Yuanji Huang, Shengyan Pu, Mengyu Huang, Chenfeng Wang, Junxi Qian, Xumin Hou, Liang Fang, Ben He, Xu-Yun Zhao

{"title":"Loss of the cardiac-enriched mitochondrial transporter SLC25A34 promotes heart failure by attenuating fatty acid oxidation.","authors":"Jieyuan Xue, Yin Long, Jiayu Zhou, Yuxuan Chen, Yuanji Huang, Shengyan Pu, Mengyu Huang, Chenfeng Wang, Junxi Qian, Xumin Hou, Liang Fang, Ben He, Xu-Yun Zhao","doi":"10.1093/jmcb/mjag026","DOIUrl":"https://doi.org/10.1093/jmcb/mjag026","url":null,"abstract":"Heart failure is characterized by profound structural and metabolic remodeling. Members of the solute carrier family 25 (SLC25), as inner mitochondrial membrane proteins, play critical roles in mitochondrial dysfunction during heart failure; however, the role of cardiac-enriched SLC25 family members remains incompletely understood. In this study, we identify solute carrier family 25 member 34 (SLC25A34) as a previously unrecognized mitochondrial regulator of cardiac energy metabolism in heart failure. SLC25A34 is highly enriched in the heart and predominantly expressed in adult cardiomyocytes. Its expression progressively increases during postnatal cardiac development, is closely associated with fatty acid-based energy utilization, and is inducible by palmitate. In contrast, SLC25A34 expression is markedly reduced in failing human hearts and multiple mouse models of heart failure. Mechanistically, oxidative stress during heart failure suppresses SLC25A34 expression in cardiomyocytes. Genetic deletion of Slc25a34 exacerbates cardiac dysfunction and adverse remodeling following transverse aortic constriction, without significantly affecting cardiac hypertrophy. Integrated biochemical, transcriptomic, and functional analyses demonstrate that loss of SLC25A34 suppresses the AMPK-CPT1B axis, thereby impairing fatty acid oxidation, leading to reduced ATP production, lipid droplet accumulation, and disrupted redox homeostasis. Conversely, adeno-associated virus-mediated cardiac-specific overexpression of Slc25a34 significantly mitigates heart failure progression. Collectively, these findings establish SLC25A34 as a key mitochondrial regulator linking fatty acid metabolism, energy sensing, and redox homeostasis and suggest that targeting SLC25A34 may represent a novel therapeutic strategy for heart failure.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701511","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}

引用次数: 0

APLN: A Promising Diagnostic and Prognostic Biomarker in Hepatocellular Carcinoma. APLN：一种有希望的肝细胞癌诊断和预后生物标志物。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-07-22 DOI: 10.1093/jmcb/mjag018

Jiwu Guo, Wenzhang Wu, Yujing Qi, Lingyun Guo, Jie Mao, Yumin Li

引用次数: 0

Endometrial gland secretome maintains the homeostasis of decidualization. 子宫内膜腺分泌组维持去个体化的稳态。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-07-17 DOI: 10.1093/jmcb/mjag023

Leqian Lin, Xintong Li, Yimeng Li, Jianlin Li, Kunfeng Bai, Kun Wang, Qingqing Zhang, Yu Li, William S B Yeung, Jian Zhang, Yuanqing Yao, Cheuk-Lun Lee, Philip C N Chiu

{"title":"Endometrial gland secretome maintains the homeostasis of decidualization.","authors":"Leqian Lin, Xintong Li, Yimeng Li, Jianlin Li, Kunfeng Bai, Kun Wang, Qingqing Zhang, Yu Li, William S B Yeung, Jian Zhang, Yuanqing Yao, Cheuk-Lun Lee, Philip C N Chiu","doi":"10.1093/jmcb/mjag023","DOIUrl":"https://doi.org/10.1093/jmcb/mjag023","url":null,"abstract":"Decidualization of human endometrial stromal cells (hESCs) during the secretory phase is critical for implantation and pregnancy. In this study, we assessed 25 established in vitro decidualization markers using in vivo single-cell transcriptomic data and found that the expression levels of most of them, including PRL and IGFBP1, were comparable between the proliferative- and secretory-phase hESCs or between the decidualized and non-decidualized hESCs. We hypothesized that the lack of endometrial glands in vitro causes the discrepancy. However, the role of the endometrial glands in decidualization remains unclear. Using a co-culture model, we demonstrated that the secretome of human endometrial organoids attenuates decidualization by reducing canonical marker upregulation and hESC mesenchymal-epithelial transition. Transcriptomic analysis revealed the downregulation of key decidualization regulators CEBPA and EDN1. Consistent with the in vitro findings, an estradiol-stimulated mouse model with increased glandular formation showed reduced decidualization. Collectively, our results identify a novel homeostatic function of endometrial gland secretome in decidualization regulation.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471231","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}

引用次数: 0

Decoding SHP2 mutations by computational saturation mutagenesis. 利用计算饱和诱变技术解码SHP2突变。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-07-17 DOI: 10.1093/jmcb/mjag022

Chen Wang, Xiao Tang, Qiaobin Yao, Ao Qi, Jie Zheng, Xingxu Huang, Shaolei Teng, Gaofeng Fan

{"title":"Decoding SHP2 mutations by computational saturation mutagenesis.","authors":"Chen Wang, Xiao Tang, Qiaobin Yao, Ao Qi, Jie Zheng, Xingxu Huang, Shaolei Teng, Gaofeng Fan","doi":"10.1093/jmcb/mjag022","DOIUrl":"https://doi.org/10.1093/jmcb/mjag022","url":null,"abstract":"Src-homology-2-containing protein tyrosine phosphatase 2 (SHP2), encoded by the PTPN11 gene, is a master regulator of cell growth, survival, and differentiation. Normally, SHP2 is kept in a self-inhibited state, in which its N-terminal SH2 domain blocks the catalytic site. SHP2 activation is directly tied to the disruption of the self-inhibition. While mutations that disrupt this self-inhibited state can cause developmental disorders and cancer, most SHP2 variants remain functionally uncharacterized. Using computational saturation mutagenesis, we systematically analyzed > 9000 single-amino acid substitutions in the SH2 and PTP domains. Our analysis of binding energy changes identified key residues-especially A72 and G503-whose mutation destabilizes the autoinhibited conformation. Functional assays further demonstrated that mutations within the SH2 and PTP domains significantly enhance enzymatic activity, downstream signaling, and cellular proliferation. By integrating clinical data, we found that pathogenic variants preferentially adopt the destabilizing conformations, directly linking structural changes to disease. This work provides a comprehensive map of SHP2 mutation effects, highlights conformational opening as a key driver of pathogenicity, and establishes a predictive framework for interpreting the functional impact of uncharacterized variants in multi-domain proteins.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471204","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}

引用次数: 0

Cytosolic transmembrane helices enter the ER membrane through EMC6-driven electrostatic interactions. 胞质跨膜螺旋通过emc6驱动的静电相互作用进入内质网膜。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-07-07 DOI: 10.1093/jmcb/mjag021

Hongyan Zheng, Wenxue Gu, Tong Zhou, Cecilia M Canessa

{"title":"Cytosolic transmembrane helices enter the ER membrane through EMC6-driven electrostatic interactions.","authors":"Hongyan Zheng, Wenxue Gu, Tong Zhou, Cecilia M Canessa","doi":"10.1093/jmcb/mjag021","DOIUrl":"https://doi.org/10.1093/jmcb/mjag021","url":null,"abstract":"The endoplasmic reticulum membrane protein complex (EMC) facilitates transmembrane domain (TMD) insertion and translocation of small terminal domains. Here, we identify EMC as a critical determinant of epithelial sodium channel (ENaC) biosynthesis. EMC loss reduces ENaC expression without affecting surface trafficking, indicating a biosynthetic stabilizing role. We demonstrate that electrostatic interactions between the negatively charged distal segment of ENaC's TMD2 and a positively charged patch on EMC6 are essential for ENaC-EMC association. We propose a 'semi-insertase' mechanism wherein the Sec61 translocon partially inserts TMD2, leaving its hydrophilic distal segment exposed to the cytosol. EMC captures this segment through electrostatic attraction and completes membrane integration. Bioinformatic analysis identified a group of non-canonical EMC clients including >200 multipass proteins with similarly charged TMDs, suggesting that electrostatic capture may represent a solution for inserting unconventional hydrophilic transmembrane segments. Additionally, we demonstrate that EMC8 plays an essential role in stabilizing the EMC-a function that cannot be compensated by its homolog EMC9 due to lower expression and absence of compensatory upregulation in EMC8-deficient cells. These results reveal a multifaceted EMC mechanism coupling insertase activity with chaperone-like stabilization to facilitate biogenesis of multipass membrane proteins containing highly hydrophilic TMDs.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396839","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}

引用次数: 0

A protein-based prediction model for fragility fracture risk in individuals with diabetes. 糖尿病患者脆性骨折风险的蛋白质预测模型

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-07-03 DOI: 10.1093/jmcb/mjaf058

Suna Wang, Li Shen, Weituo Zhang, Jingyi Guo, Wei Chen, Xiangtian Yu, Cheng Hu

{"title":"A protein-based prediction model for fragility fracture risk in individuals with diabetes.","authors":"Suna Wang, Li Shen, Weituo Zhang, Jingyi Guo, Wei Chen, Xiangtian Yu, Cheng Hu","doi":"10.1093/jmcb/mjaf058","DOIUrl":"10.1093/jmcb/mjaf058","url":null,"abstract":"Individuals with diabetes are at high risk of fragility fractures. We aimed to develop and validate a protein-based model to predict fragility fractures in individuals with diabetes and to explore whether a protein risk score (ProRS) would improve the risk prediction. A total of 3535 individuals with diabetes from the UK Biobank Pharma Proteomics Project were included in the study. During a median follow-up period of 13.3 years, 5.2% (185) of the individuals with diabetes experienced a fragility fracture. Of 2902 unique proteins, 139 exhibited significant associations with fragility fracture risk. A protein-based model that included 10 proteins was then developed using the machine learning model. Compared with the low ProRS tertile, medium and high tertiles were strongly associated with increased fragility fracture risk. The ProRS achieved a C-index of 0.739 and a 10-year area under the curve (AUC) of 0.733 for the fragility fracture prediction. Adding ProRS to the traditional prediction model (the fracture risk assessment tool [FRAX]) improved the prediction performance with a C-index increase of 0.080 (0.673 [FRAX] vs. 0.754 [FRAX+ProRS]) and a 10-year AUC increase of 0.064 (0.693 vs. 0.757), thereby promoting early monitoring and prevention in individuals with diabetes.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13395793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900579","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}

引用次数: 0

Transcriptional co-activators YAP/TAZ in cancer-associated fibroblasts are dispensable for Notch-driven intrahepatic cholangiocarcinoma. 癌症相关成纤维细胞中的转录共激活因子YAP/TAZ对于缺口驱动的肝内胆管癌是必不可少的。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-07-03 DOI: 10.1093/jmcb/mjag010

Tingting Deng, Yuemei Qiao, Xinyu Xie, Yanjun Wu, Gaoxiang Ge

引用次数: 0