LYRM4

更新于：2025-05-07

基本信息

别名

C6orf149、CGI-203、ISD11

+ [3]

简介

Stabilizing factor, of the core iron-sulfur cluster (ISC) assembly complex, that regulates, in association with NDUFAB1, the stability and the cysteine desulfurase activity of NFS1 and participates in the [2Fe-2S] clusters assembly on the scaffolding protein ISCU (PubMed:17331979, PubMed:31664822). The core iron-sulfur cluster (ISC) assembly complex is involved in the de novo synthesis of a [2Fe-2S] cluster, the first step of the mitochondrial iron-sulfur protein biogenesis. This process is initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1) that produces persulfide which is delivered on the scaffold protein ISCU in a FXN-dependent manner. Then this complex is stabilized by FDX2 which provides reducing equivalents to accomplish the [2Fe-2S] cluster assembly. Finally, the [2Fe-2S] cluster is transferred from ISCU to chaperone proteins, including HSCB, HSPA9 and GLRX5 (By similarity). May also participates in the iron-sulfur protein biogenesis in the cytoplasm through its interaction with the cytoplasmic form of NFS1 (PubMed:19454487).

关联

100 项与 LYRM4 相关的临床结果

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100 项与 LYRM4 相关的转化医学

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0 项与 LYRM4 相关的专利（医药）

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项与 LYRM4 相关的文献（医药）

2025-05-01·Surgery

Mitochondrial-related genome-wide Mendelian randomization identifies putatively causal genes in the pathogenesis of sepsis

Review

作者: Sun, Jiaojiao ; Burgess, Smith ; Wang, Zhiqiang ; Wu, Yaxian ; Weng, Yuan

BACKGROUNDThe dysfunction of mitochondria has been associated with the development of sepsis, but the specific mitochondrial-related genes and their roles in sepsis have not been fully elucidated. We employed Mendelian randomization and colocalization analysis to investigate the association between mitochondrial-related genes and sepsis by integrating multi-omics data.METHODSSummary-level data on mitochondrial gene methylation, expression, and protein abundance levels were obtained from corresponding studies on methylation, expression, and protein quantitative trait loci, respectively. Genetic associations with sepsis were obtained from the genome-wide association studies catalog database. We used the MitoCarta3.0 database, which contains an updated list of 1,136 human mitochondrial genes, to identify mitochondrial genes. To assess the associations between mitochondrial gene-related molecular features and sepsis, we conducted summary data-based Mendelian randomization analysis. In addition, we performed colocalization analysis to determine whether the identified signal pairs shared a causal genetic variant.RESULTSAfter integrating the multi-omics data between methylation quantitative trait loci- expression quantitative trait loci and expression quantitative trait loci-protein quantitative trait loci, we identified FIS1 as having tier 1 evidence for its association with sepsis. Methylation of cg01299997 in FIS1 was found to be associated with lower expression of FIS1, an increased risk of sepsis, and a positive role in cg01299997 methylation. Furthermore, NUDT2, IMMP2L, LYRM4, MRPL10, MRPL17, MTIF3, and TFAM genes were associated with sepsis risk with tier 2 evidence. Both gene expression and protein abundance levels of NUDT2 were observed to be associated with an increased risk of sepsis. In addition, the ATP5MC1 and VWA8 genes were associated with sepsis risk with tier 3 evidence. Among these tertiary genes, ATP5MC1 gene expression level showed a negative correlation (posterior probability of H4 = 0.9242), whereas the gene expression level of VWA8 exhibited a positive correlation (posterior probability of H4 = 0.7270).CONCLUSIONWe found that the mitochondrial FIS1, NUDT2, IMMP2L, LYRM4, MRPL10, MRPL17, MTIF3, TFAM, ATP5MC1, and VWA8 genes were putatively associated with sepsis risk with evidence from multi-omics levels. This study identified mitochondrial genes in relation to sepsis, which may enhance the understanding of the pathogenic mechanisms of sepsis development.

2025-04-01·Translational Research

Multi-Omics Analysis Links Mitochondrial-Related Genes to Idiopathic Pulmonary Fibrosis and In Vivo Transcriptome Validation

Article

作者: Guan, Bingyue ; Yang, Minghuan ; Zhang, Mingwei ; Lin, Qiaojing ; Huang, Xingxin ; Li, Lianhuang ; Li, Xiaoxia ; Chen, Chun ; Hong, Jinsheng

Mitochondrial dysfunction is closely associated with idiopathic pulmonary fibrosis (IPF). However, the causal association between mitochondria-related genes and IPF remains to be determined. We obtained gene expression, protein abundance, and methylation quantitative trait locus data for mitochondria-related genes from previous studies. Genome-wide association study data for patients with IPF were obtained from the FinnGen study. A two-sample Mendelian randomisation analysis was conducted to assess the association between mitochondria-related genes and IPF. Furthermore, we conducted validation of expression differences utilizing transcriptome data derived from the BLM-induced pulmonary fibrosis mouse model (n=15). Concurrently, multiphoton imaging was utilized to quantify collagen contents and structural assessment. The direction of causality was verified using the Steiger test, and colocalisation analysis was used to better validate causality. Single-cell data were used to explore the localisation and expression of positive genes across different cell types. The study identified significant associations between mitochondria-related genes and IPF, with POLG and NDUFB10 classified as Grade 1; LYRM4, NBR1, and ACSF3 as Grade 2; MCL1, GFER, MFN2, IVD, and SLC25A35 as Grade 3; and METAP1D and MTX1 as Grade 4. Single-cell analysis showed elevated expression of NBR1, MCL1, and MTX1 in pulmonary myofibroblasts of IPF. This study elucidated the causal effects of mitochondria-related genes on IPF, underscoring their significance in pathogenesis. These findings contribute to an improved understanding of the mechanisms underlying IPF, offering new potential therapeutic targets for interventions.

2025-02-18·Biochemistry

Frataxin Traps Low Abundance Quaternary Structure to Stimulate Human Fe–S Cluster Biosynthesis

Article

作者: Patra, Shachin ; Shirzadeh, Mehdi ; Cory, Seth A. ; Russell, David H. ; Putnam, Christopher D. ; Havens, Steven M. ; Lin, Cheng-Wei ; Barondeau, David P.

Iron-sulfur clusters are essential protein cofactors synthesized in human mitochondria by an NFS1-ISD11-ACP-ISCU2-FXN assembly complex. Surprisingly, researchers have discovered three distinct quaternary structures for cysteine desulfurase subcomplexes, which display similar interactions between NFS1-ISD11-ACP protomeric units but dramatically different dimeric interfaces between the protomers. Although the role of these different architectures is unclear, possible functions include regulating activity and promoting the biosynthesis of distinct sulfur-containing biomolecules. Here, crystallography, native ion-mobility mass spectrometry, and chromatography methods reveal the Fe-S assembly subcomplex exists as an equilibrium mixture of these different quaternary structures. Isotope labeling and native mass spectrometry experiments show that the NFS1-ISD11-ACP complexes disassemble into protomers, which can then undergo exchange reactions and dimerize to reform native complexes. Single crystals isolated in distinct architectures have the same activity profile and activation by the Friedreich's ataxia (FRDA) protein frataxin (FXN) when rinsed and dissolved in assay buffer. These results suggest FXN functions as a "molecular lock" and shifts the equilibrium toward one of the architectures to stimulate the cysteine desulfurase activity and promote iron-sulfur cluster biosynthesis. An NFS1-designed variant similarly shifts the equilibrium and partially replaces FXN in activating the complex. We propose that eukaryotic cysteine desulfurases are unusual members of the morpheein class of enzymes that control their activity through their oligomeric state. Overall, the findings support architectural switching as a regulatory mechanism linked to FXN activation of the human Fe-S cluster biosynthetic complex and provide new opportunities for therapeutic interventions of the fatal neurodegenerative disease FRDA.

项与 LYRM4 相关的新闻（医药）

2025-04-29

·今日头条

最全面研究！华科大&武大团队破解肺癌防治密码，精准干预新时代来临

【导读】新出现的证据强调了APA在基因转录后调控中的关键作用，与 APA 相关的遗传变异（apaQTLs）对多种疾病具有特别重要的意义。然而，APA 的遗传调控及其在非小细胞肺癌（NSCLC）风险中的作用尚未得到充分研究。 4月26日，华中科技大学/武汉大学研究人员合作共同在期刊《Advanced Science》上发表了研究论文，题为“Genetic Regulation of Alternative Polyadenylation Provides Novel Insights into Molecular Mechanisms Underlying Non-small Cell Lung Cancer”，本研究中，研究人员通过利用来自癌症基因组图谱的基因型和 APA 数据，在非小细胞肺癌样本中确定了遗传变异与 APA 之间的关联。值得注意的是，将 apaQTL 变异与传统 GWAS 衍生的 PRS 集成被证明是筛查非小细胞肺癌的潜在工具。从机制上讲，rs9606 通过等位基因特异性与 NUDT21 相互作用诱导 LYRM4 的异常 APA 过程，从而导致癌基因 LYRM4 表达增加，进而增加非小细胞肺癌风险。本研究证明了与 APA 相关的遗传变异在非小细胞肺癌风险中的独特贡献，为非小细胞肺癌的病因学和临床干预提供了关键线索和潜在靶点。 https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202502008 背景知识 01 肺癌仍是全球最常见的癌症之一，也是癌症相关死亡的首要原因，对人类健康构成严重威胁。非小细胞肺癌（NSCLC）是最常见的类型，占所有肺癌病例的 85%。众所周知，除了环境风险因素（如吸烟）外，基因变异也会增加患非小细胞肺癌的风险。GWAS已确定了众多与非小细胞肺癌风险相关的基因变异，但确定因果变异并阐明其功能机制仍是一项持续的挑战。据估计，近 70% 的人类基因具有多个多聚腺苷酸化位点，会发生 APA。通过使用不同的多聚（A）位点，APA 会产生具有不同 3'非翻译区（UTR）长度的转录本。由于 3'UTR 包含 RNA 结合蛋白（RBP）和 miRNA 的调节元件，APA 可通过改变 mRNA 稳定性、翻译效率或蛋白质的细胞定位来调节基因表达。已知 APA 在癌症中显著失调。异常 APA 是多种癌症的常见特征，并导致癌基因和肿瘤抑制基因的失调。此外，关键 APA 调节因子的表达改变通常会全局改变 APA，并扰乱与癌症相关的生物过程，包括细胞周期、细胞凋亡和增殖。尽管有这些观察结果，但研究人员对诱导异常 APA 的潜在机制仍知之甚少。 apaQTLs 目标基因在癌症发展和治疗中发挥关键作用 02 根据apaQTL 分析，研究人员共鉴定出 2037 个基因和 2109 个相关的 APA 事件。研究人员首先对 aGenes 进行了通路富集分析。研究人员接下来基于 TCGA 的数据评估了 NSCLC 中的 SCNA。鉴于免疫细胞在调节癌症发展中的新兴作用，研究人员进一步评估了它们与 aGene 表达的关联，其中免疫细胞浸润数据使用 TIMER 和 EPIC 算法进行量化。结果表明，多个 aGenes与特定的免疫细胞亚群相关，包括 CD8+T 细胞、CD4+T 细胞和巨噬细胞。为了了解 aGenes对药物反应的影响，研究人员利用GDSC数据进行了系统的药物基因组学分析，共鉴定出 34902 个显著相关的 aGenes - 药物配对。研究人员重点关注与 aGenes高度相关的药物及其药物靶点。值得注意的是，排名靠前的药物类别是靶向 ERK/MAPK 信号通路的药物，包括曲美替尼和达拉非尼，这两种药物已获美国食品药品监督管理局（FDA）批准联合用于非小细胞肺癌（NSCLC）的治疗。综上所述，上述分析结果表明 apaQTLs 目标基因在癌症发展和治疗中具有独特的作用。结论 03 本研究发现可能有助于增进对基因变异与非小细胞肺癌易感性之间分子机制的理解，并最终改善非小细胞肺癌的精准预防和治疗策略。参考资料： https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202502008 【关于投稿】转化医学网（360zhyx.com）是转化医学核心门户，旨在推动基础研究、临床诊疗和产业的发展，核心内容涵盖组学、检验、免疫、肿瘤、心血管、糖尿病等。如您有最新的研究内容发表，欢迎联系我们进行免费报道（公众号菜单栏-在线客服联系），我们的理念：内容创造价值，转化铸就未来！转化医学网（360zhyx.com）发布的文章旨在介绍前沿医学研究进展，不能作为治疗方案使用；如需获得健康指导，请至正规医院就诊。责任声明：本稿件如有错误之处，敬请联系转化医学网客服进行修改事宜！微信号：zhuanhuayixue 热门推荐活动点击免费报名 🕓 浙江｜2025年5月9日 ▶ 首届精准医学国际学术研讨会暨队列研究先锋计划颁奖仪式 🕓 上海｜2025年6月12-15日 ▶ 第七届上海国际癌症大会暨第十八届全国医学生物技术研讨会暨第六届中德双边论坛 🕓 上海｜2025年7月17-18日 ▶ 第四届长三角体外诊断产业高峰论坛 🕓 北京｜2025年9月19-20日 ▶ 第六届单细胞技术应用研讨会暨空间组学前沿研讨会 🕓 上海｜2025年11月14-15日 ▶ 第二届中国类器官转化医学大会点击对应文字查看详情

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