更新于：2024-09-19

UQCRQ

更新于：2024-09-19

基本信息

别名

Complex III subunit 8、Complex III subunit VIII、Cytochrome b-c1 complex subunit 8

+ [7]

简介

Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. The cytochrome b-c1 complex catalyzes electron transfer from ubiquinol to cytochrome c, linking this redox reaction to translocation of protons across the mitochondrial inner membrane, with protons being carried across the membrane as hydrogens on the quinol. In the process called Q cycle, 2 protons are consumed from the matrix, 4 protons are released into the intermembrane space and 2 electrons are passed to cytochrome c.

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100 项与 UQCRQ 相关的临床结果

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100 项与 UQCRQ 相关的转化医学

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0 项与 UQCRQ 相关的专利（医药）

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130

项与 UQCRQ 相关的文献（医药）

2024-04-01·Current Medical Science

Cardioprotective Potential of Cymbopogon citratus Essential Oil against Isoproterenol-induced Cardiomyocyte Hypertrophy: Possible Involvement of NLRP3 Inflammasome and Oxidative Phosphorylation Complex Subunits

Article

作者: Zhang, Hao ; Tang, Xi-Lan ; Li, Ting-Ting ; Dong, Wei ; Xiong, Zheng-Yu ; He, Chun-Ni ; Qiu, Yu-Mei ; Xie, Meng-Die ; Wang, Hu ; Ding, Xiao-Yun

OBJECTIVECymbopogon citratus (DC.) Stapf is a medicinal and edible herb that is widely used for the treatment of gastric, nervous and hypertensive disorders. In this study, we investigated the cardioprotective effects and mechanisms of the essential oil, the main active ingredient of Cymbopogon citratus, on isoproterenol (ISO)-induced cardiomyocyte hypertrophy.METHODSThe compositions of Cymbopogon citratus essential oil (CCEO) were determined by gas chromatography-mass spectrometry. Cardiomyocytes were pretreated with 16.9 µg/L CCEO for 1 h followed by 10 µmol/L ISO for 24 h. Cardiac hypertrophy-related indicators and NLRP3 inflammasome expression were evaluated. Subsequently, transcriptome sequencing (RNA-seq) and target verification were used to further explore the underlying mechanism.RESULTSOur results showed that the CCEO mainly included citronellal (45.66%), geraniol (23.32%), and citronellol (10.37%). CCEO inhibited ISO-induced increases in cell surface area and protein content, as well as the upregulation of fetal gene expression. Moreover, CCEO inhibited ISO-induced NLRP3 inflammasome expression, as evidenced by decreased lactate dehydrogenase content and downregulated mRNA levels of NLRP3, ASC, CASP1, GSDMD, and IL-1β, as well as reduced protein levels of NLRP3, ASC, pro-caspase-1, caspase-1 (p20), GSDMD-FL, GSDMD-N, and pro-IL-1β. The RNA-seq results showed that CCEO inhibited the increase in the mRNA levels of 26 oxidative phosphorylation complex subunits in ISO-treated cardiomyocytes. Our further experiments confirmed that CCEO suppressed ISO-induced upregulation of mt-Nd1, Sdhd, mt-Cytb, Uqcrq, and mt-Atp6 but had no obvious effects on mt-Col expression.CONCLUSIONCCEO inhibits ISO-induced cardiomyocyte hypertrophy through the suppression of NLRP3 inflammasome expression and the regulation of several oxidative phosphorylation complex subunits.

2024-03-01·Science of The Total Environment

Triclosan and its alternatives, especially chlorhexidine, modulate macrophage immune response with distinct modes of action

Article

作者: Rossol, Manuela ; von Bergen, Martin ; Karkossa, Isabel ; Schubert, Kristin ; Raps, Stefanie ; Bahr, Laura

Since European regulators restricted the use of bacteriocidic triclosan (TCS), alternatives for TCS are emerging. Recently, TCS has been shown to reprogram immune metabolism, trigger the NLRP3 inflammasome, and subsequently the release of IL-1β in human macrophages, but data on substitutes is scarce. Hence, we aimed to examine the effects of TCS compared to its alternatives at the molecular level in human macrophages. LPS-stimulated THP-1 macrophages were exposed to TCS or its substitutes, including benzalkonium chloride, benzethonium chloride, chloroxylenol, chlorhexidine (CHX) and cetylpyridinium chloride, with the inhibitory concentration (IC₁₀-value) of cell viability to decipher their mode of action. TCS induced the release of the pro-inflammatory cytokine TNF and high level of IL-1β, suggesting the activation of the NLRP3-inflammasome, which was confirmed by non-apparent IL-1β under the NLRP3-inhibitor MCC950 treatment d. While IL-6 release was reduced in all treatments, the alternative CHX completely abolished the release of all investigated cytokines. To unravel the underlying molecular mechanisms, we used untargeted LC-MS/MS-based proteomics. TCS and CHX showed the strongest cellular response at the protein and signalling pathway level, whereby pathways related to metabolism, translation, cellular stress and migration were mainly affected but to different proposed modes of action. TCS inhibited mitochondrial electron transfer and affected phagocytosis. In contrast, in CHX-treated cells, the translation was arrested due to stress conditions, resulting in the formation of stress granules. Mitochondrial (e.g. ATP5F1D, ATP5PB, UQCRQ) and ribosomal (e.g. RPL10, RPL35, RPS23) proteins were revealed as putative key drivers. Furthermore, we have demonstrated the formation of podosomes by CHX, potentially involved in ECM degradation. Our results exhibit modulation of the immune response in macrophages by TCS and its substitutes and illuminated underlying molecular effects. These results illustrate critical processes involved in the modulation of macrophages' immune response by TCS and its alternatives, providing information essential for hazard assessment.

2023-11-17·Medicine

NDUFB11 and NDUFS3 regulate arterial atherosclerosis and venous thrombosis: Potential markers of atherosclerosis and venous thrombosis

Article

作者: Chen, Qing-Liang ; Guo, Su-Zhi ; Yang, Yin ; Ma, Yan-Hong ; Li, Jing-Hui ; Wang, Lian-Qun ; Guo, Zhi-Gang ; Yao, Bo-Chen

Atherosclerosis is a chronic disease that thickens the blood vessel walls and narrows the lumen. Venous thrombosis is a blood clot that forms in the body’s deep veins or pulmonary arteries. However, the relationship between NDUFB11 and NDUFS3 and atherosclerosis and venous thrombosis is unclear. We employed data files that combined atherosclerosis and chronic stress groups. Subsequently, we conducted differential gene expression analysis (DEGs) and performed weighted gene co-expression network analysis (WGCNA). We constructed and analyzed a protein-protein interaction (PPI) network. Further analyses included functional enrichment analysis, gene set enrichment analysis (GSEA), gene expression heatmaps, immune infiltration analysis, and mRNA analysis. By comparing our findings with the Comparative Toxicogenomics Database (CTD), we identified the most relevant diseases associated with the core genes. Additionally, we utilized TargetScan to screen for miRNAs regulating the central DEGs. To validate our results, we conducted Western Blot experiments at the cellular level. A total of 1747 DEGs were co-identified. According to the Gene Ontology (GO) analysis of differentially expressed genes, they were primarily enriched in mitochondrial gene expression, mitochondrial envelope, organelle membrane, and mitochondrial inner membrane categories. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the target cells were mainly enriched in metabolic pathways, ribosomes, and histidine metabolism. The intersection of enriched terms from both GO and KEGG analyses showed significant enrichment in mitochondrial gene expression, mitochondrial envelope, organelle inner membrane, ribosomal structural constituents, histidine metabolism, and oxidative phosphorylation. Eight core genes were identified, including NDUFS5, UQCRQ, COX6C, COX7B, ATP5ME, NDUFS3, NDUFA3, and NDUFB11. The gene expression heatmap demonstrated that core genes (NDUFB11 and NDUFS3) were downregulated in atherosclerosis with venous thrombosis samples and upregulated in normal samples. CTD analysis revealed that the core genes NDUFB11 and NDUFS3 were associated with pain, arterial diseases, atherosclerosis, arteritis, venous thrombosis formation, and venous thromboembolism. We added Western Blot basic cell experiment for verification. NDUFB11 and NDUFS3 are downregulated in atherosclerosis and venous thrombosis, associated with poorer prognosis, and may serve as potential biomarkers for both diseases.

项与 UQCRQ 相关的新闻（医药）

2024-06-17

·生物探索

Science丨王逊等揭示线粒体代谢的不灵活性保护再生肝脏健康

引言线粒体作为细胞内的能量代谢细胞器，其功能障碍与一系列肝脏病变相关。在脂肪肝，肝硬化和肝衰竭等疾病中，均发现线粒体电子传递链 (ETC) 复合物的活性被抑制，线粒体膜电位下降等问题【1-4】。肝脏作为再生能力极强的器官，但是其再生过程中，线粒体的功能尚不明确。 2024年6月14日，德克萨斯大学西南医学中心Prashant Mishra实验室的博士后王逊等在Science杂志发表了题为Metabolic inflexibility promotes mitochondrial health during liver regeneration的研究论文，发现肝脏再生过程中，线粒体通过其代谢的不灵活性，保护再生肝脏健康。作者首先在分离的再生肝脏线粒体中发现，脂肪酸和酮体的含量增加。肝脏是一个区域性器官，不同区域其再生能力存在差异【5, 6】。作者发现不同区域线粒体中脂肪酸和酮体增加比例与其区域的再生能力呈正相关。通过同位素示踪发现，再生的肝脏中，[U-13C]棕榈酸被代谢产生更多的β-羟基丁酸(M+2)和乙酰辅酶A(M+2)，以及在分离的原代的再生肝细胞中，[1-14C]棕榈酸会被代谢产生更多的[14C]二氧化碳。提示肝脏再生过程中，肝脏脂肪代谢能力上升。脂肪酸氧化主要在线粒体进行，β-氧化过程中，产生NADH和FADH2，随后被线粒体ETC氧化。线粒体ETC由5个复合物组成，为了验证线粒体ETC在其中作用，作者选取 Ndufa9f/f (复合物I)，Sdhaf/f (复合物II)，Uqcrqf/f (复合物III)，Cox10f/f (复合物IV) 和 Atp5f1af/f (复合物V)，5个品系老鼠，通过AAV注射，分别特异性地阻断肝细胞的电子传输。作者发现，经过70%肝脏切除术诱导肝脏再生后，野生型和Ndufa9缺失的肝脏再生正常，Sdha，Uqcrq 或Atp5f1a缺失的肝脏无法再生，并且老鼠在术后1-2天内全部死亡。 Cox10缺失的肝脏无法再生，但是老鼠全部存活，同时有大量的脂肪堆积。先前，谢渭芬实验室和惠利健实验室【7】，以及周斌实验室和Jan S. Tchorz实验室【8】研究揭示，胆管细胞在特定条件下，可转分化为肝细胞。经过作者分析，Cox10缺失的肝脏中，胆管细胞经过转分化，成为肝细胞，以支持肝脏再生。作者为了探寻肝脏中堆积的脂肪来源，使用同位素示踪发现，经过重水(D2O)处理后，肝脏再生过程中，肝细胞内的脂肪并不由其自身合成，而是来自外周脂肪组织的分解。先前丁秋蓉实验室报道【9】，肝脏再生过程中，外周脂肪分解产生的脂肪酸转运进入肝脏，通过影响MIER1蛋白水平，进而影响肝脏再生。β-氧化的重要产物之一是乙酰辅酶A，作者利用代谢组学检测，Cox10缺失的肝脏中，乙酰辅酶A水平显著低于正常肝脏。乙酰辅酶A对组蛋白乙酰化修饰不可或缺。作者利用CHIP-seq发现，组蛋白乙酰化水平下降，导致与细胞周期有关的基因表达下降，进而影响肝脏再生。肝脏中乙酰辅酶A的来源不止于脂肪酸，葡萄糖和乙酸为什么不能产生乙酰辅酶A？作者发现，脂肪的堆积提升肝细胞的PDK4表达，而PDK4的上升，通过磷酸化PDH，抑制丙酮酸到乙酰辅酶A的转化。脂肪的堆积同时降低肝细胞的ACSS1/2蛋白水平，进而抑制乙酸转化为乙酰辅酶A。为确认葡萄糖来源和乙酸来源的乙酰辅酶A转化是否受到抑制，作者利用同位素示踪，通过[U-13C]葡萄糖或[U-13C]乙酸钠发现，Cox10缺失的肝脏中，乙酰辅酶A(M+2)/ 丙酮酸(M+3)或乙酰辅酶A(M+2)/ 乙酸(M+2)的比值显著下降，提示由葡萄糖或者乙酸合成乙酰辅酶A的能力下降。作者为验证PDK4在其中的作用，利用CRISPR-Cas9技术和抑制剂处理肝脏，发现Pdk4缺失或者被抑制时，线粒体ETC缺失的肝细胞进行增殖。外周脂肪组织分解，产生的脂肪酸通过β-氧化，支持正常肝细胞增殖。线粒体ETC缺失的肝细胞，无法利用脂肪酸，使其堆积，进而抑制丙酮酸到乙酰辅酶A的转化，使其无法增殖。当PDK4被抑制时，线粒体ETC缺失的肝细胞，通过利用丙酮酸来源的乙酰辅酶A进行增殖。(Credit: Science) 综上所述，本研究发现肝脏再生过程中，肝脏利用其代谢的不灵活性，通过脂质积累，抑制线粒体ETC功能障碍的肝细胞的增殖，以保护肝脏健康。参考文献 1. C. Koliaki et al., Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis. Cell Metab 21, 739-746 (2015). 2. M. Perez-Carreras et al., Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis. Hepatology 38, 999-1007 (2003). 3. H. Cortez-Pinto et al., Alterations in liver ATP homeostasis in human nonalcoholic steatohepatitis: a pilot study. JAMA 282, 1659-1664 (1999). 4. B. Fromenty, M. Roden, Mitochondrial alterations in fatty liver diseases. J Hepatol 78, 415-429 (2023). 5. L. He et al., Proliferation tracing reveals regional hepatocyte generation in liver homeostasis and repair. Science 371, (2021). 6. Y. Wei et al., Liver homeostasis is maintained by midlobular zone 2 hepatocytes. Science 371, (2021). 7. X. Deng et al., Chronic Liver Injury Induces Conversion of Biliary Epithelial Cells into Hepatocytes. Cell Stem Cell 23, 114-122 e113 (2018). 8. W. Pu et al., Bipotent transitional liver progenitor cells contribute to liver regeneration. Nat Genet 55, 651-664 (2023). 9. Y. Chen et al., Acute liver steatosis translationally controls the epigenetic regulator MIER1 to promote liver regeneration in a study with male mice. Nat Commun 14, 1521 (2023). https://doi.org/10.1126/science.adj4301 责编|探索君排版|探索君文章来源|“BioArt” End 往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文 Cell | 是什么决定了细胞的大小？热文 Nature | 2024年值得关注的七项技术热文 Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文 CRISPR技术进化史 | 24年Cell综述

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