mSphere
·
2025
·
IF 3.1
Xinda Li,Xiaoyi Luo,Bin Wang,Lei Fu,Xi Chen,Yu Lu
Drug-resistant tuberculosis (DR-TB) urgently requires safer, more accessible alternatives to bedaquiline (BDQ), which faces critical flaws like cardiotoxicity, high costs, and emerging resistance. WX-081, a promising BDQ alternative, has demonstrated superior anti-TB activity and improved safety in clinical studies. However, its mechanism of action remains unexplored, underscoring the need for further research to optimize its potential in advancing global TB elimination efforts. This study reveals WX-081’s dual mechanisms: targeting atpE to disrupt ATP synthase and proton motive force via resistance screening, gene sequencing, and functional assays while enhancing host immunity through macrophage transcriptomics. Molecular docking confirmed atpE binding sites, and immune activation pathways (NF-κB/MAPK) were identified, positioning WX-081 as a potent, safe anti-DR-TB candidate despite unresolved mechanistic details.
研究领域:
微生物学
·
药物研发
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2023
·
IF 6.1
Ying Gao,Jie Zhang,Jiexia Pan,Sanjun Ying,Bang Lou,Qingliang Yang,Weiyong Hong,Gensheng Yang
Aims To establish a F O F1-ATP synthase molecular motor biosensor to accurately identify colon cancer miRNAs. Main methods The F O F1-ATP synthase molecular motor is extracted by fragmentation–centrifugation and connected to the colon cancer-specific miR-17 capture probe in the manner of the ε subunit-biotin-streptavidin-biotin system. Signal probes are designed for dual-signal characterization to increase detection accuracy. The F O F1-ATPase rotation rate decreases when the signaling and capture probes are combined with the target miRNA, resulting in a decrease in ATP synthesis. miR-17 concentrations are determined by changes in ATP-mediated chemiluminescence intensity and signal probe-mediated OD 450nm . Key findings The chemiluminescence intensity and OD 450nm show a good linear relationship with the miR-17 concentration in the range of 5 to 200 nmol L −1 (R 2 = 0.9985, 0.9989). The colon cancer mouse model is established for the blood samples, and miR-17 in serum and RNA extracts is quantitatively determined using the constructed sensor. Significance The results are consistent with colon cancer progression, and the low concentration of miR-17 detecting accuracy is comparable to the PCR assay. In conclusion, the developed method is a direct, rapid, and promising method for miRNA detection of colon cancer.
研究领域:
生物化学
·
分子生物学
·
癌症研究
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Yu Ma,Wei Yang,Peiyao Liang,Ruzhen Feng,Tianming Qiu,Jingyuan Zhang,Xiance Sun,Qiujuan Li,Guang Yang,Xiaofeng Yao
As a persistent organic pollutant, perfluorooctane sulfonate (PFOS) has a serious detrimental impact on human health. It has been suggested that PFOS is associated with liver inflammation. However, the underlying mechanisms are still unclear. Here, PFOS was found to elevate the oligomerization tendency of voltage-dependent anion channel 1 (VDAC1) in the mice liver and human normal liver cells L-02. Inhibition of VDAC1 oligomerization alleviated PFOS-induced nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome activation. Cytoplasmic membrane VDAC1 translocated to mitochondria was also observed in response to PFOS. Therefore, the oligomerization of VDAC1 occurred mainly in the mitochondria. VDAC1 was found to interact with the ATP synthase beta subunit (ATP5B) under PFOS treatment. Knockdown of ATP5B or immobilization of ATP5B to the cytoplasmic membrane alleviated the increased VDAC1 oligomerization and NLRP3 inflammasome activation. Therefore, our results suggested that PFOS induced NLRP3 inflammasome activation through VDAC1 oligomerization, a process dependent on ATP5B to transfer VDAC1 from the plasma membrane to the mitochondria. The findings offer novel perspectives on the activation of the NLRP3 inflammasome, the regulatory mode on VDAC1 oligomerization, and the mechanism of PFOS toxicity.
研究领域:
毒理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2017
·
IF 4.259
Xie Xiaoyun,Han Chaofei,Zeng Weiqi,Chen Chen,Lu Lixia,Liu Queping,Peng Cong,Zhao Shuang,Su Juan,Chen Xiang
The F1F0-ATP synthase, an enzyme complex, is mainly located on the mitochondrial inner membrane or sometimes cytomembrane to generate or hydrolyze ATP, play a role in cell proliferation. This study focused on the role of F1F0-ATP synthase in keratinocyte differentiation, and its relationship with intracellular and extracellular ATP (InATP and ExATP). The F1F0-ATP synthase β subunit (ATP5B) expression in various skin tissues and confluence-dependent HaCaT differentiation models was detected. ATP5B expression increased with keratinocyte and HaCaT cell differentiation in normal skin, some epidermis hyper-proliferative diseases, squamous cell carcinoma, and the HaCaT cell differentiation model. The impact of InATP and ExATP content on HaCaT differentiation was reflected by the expression of the differentiation marker involucrin. Inhibition of F1F0-ATP synthase blocked HaCaT cell differentiation, which was associated with a decrease of InATP content, but not with changes of ExATP. Our results revealed that F1F0-ATP synthase expression is associated with the process of keratinocyte differentiation which may possibly be related to InATP synthesis.
研究领域:
细胞生物学
·
分子生物学
·
皮肤病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF EXPERIMENTAL BOTANY
·
2023
·
IF 6.9
He Chengyong,Xing Fei,Liang Jiahui,Zhang Zhixiang,Zhan Binhui,Habili Nuredin,Wang Hongqing,Li Shifang
Apple necrotic mosaic virus (ApNMV) is associated with apple mosaic disease in China. However, the mechanisms of ApNMV infection, as well as host defence against the virus, are still poorly understood. Mitochondrial ATP synthase plays a fundamental role in the regulation of plant growth and development. However, mitochondrial ATP synthase function in response to virus infection remains to be defined. In the present study, a yeast two-hybrid (Y2H) screening revealed that the apple mitochondrial ATP synthase oligomycin sensitivity-conferring protein (OSCP) subunit (MdATPO) interacts with ApNMV coat protein (CP). It was further verified that overexpression of MdATPO in Nicotiana benthamiana inhibited viral accumulation. In contrast, silencing of NbATPO facilitated viral accumulation, indicating that ATPO plays a defensive role during ApNMV infection. Further investigation demonstrated that ApNMV infection accelerated abscisic acid (ABA) accumulation, and ABA negatively regulated ATPO transcription, which was related to the ability of ABA insensitive 5 (ABI5) to bind to the ABA-responsive elements (ABREs) of the ATPO promoter. Taken together, our results indicated that transcription factor ABI5 negatively regulated ATPO transcription by directly binding to its promoter, leading to the susceptibility of apple and N. benthamiana to ApNMV infection. The current study facilitates a comprehensive understanding of the intricate responses of the host to ApNMV infection.
研究领域:
植物病理学
·
分子生物学
·
病毒学
·
植物生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
·
2021
·
IF 5.645
Zhuoheng Zhong,Shengzhi Liu,Songling Han,Yaohan Li,Minglei Tao,Amin Liu,Qiang He,Sixue Chen,Criag Dufresne,Wei Zhu,Jingkui Tian
Indole alkaloids from Catharanthus roseus (L.) G. Don were valued for their wide spectrum of pharmaceutical effects. Their biosynthesis is modulated by various abiotic factors including ultraviolet B radiation which induced ATP production and led to accumulation of indole alkaloids. To investigate the regulatory mechanism of secondary metabolism in the leaf mitochondria of C. roseus under ultraviolet B radiation, combinatory study of proteomic and metabolomic analyses of C. roseus was performed. ATP export in the leaves of C. roseus increased under UVB radiation, which required mitochondrial ATP synthase. Proteins related to mitochondrial complexes II/IV and their gene expression levels increased, and those related to mitochondrial complex I decreased. Proteins related to the methylerythritol phosphate pathway, especially geranylgeranyl pyrophosphate synthase, increased under ultraviolet B radiation. Metabolites whose levels changed were mainly alkaloids, organic acids, carbohydrates, phenylpropanoids, and fatty acids, while eight indole alkaloids increased. Integrative analysis of omics data indicated that the metabolism of glutamate and tyrosine was downregulated. These results suggest that ultraviolet B radiation induces dynamic changes in mitochondria in C. roseus , which guarantees ATP production, regulates the flux of the methylerythritol phosphate pathway to the biosynthesis of monoterpene moieties, and leads to accumulation of various indole alkaloids.
研究领域:
植物生物化学
·
分子生物学
·
药理学
·
环境科学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Yize Liu,Ning Jiang,Si Zuo,Ying Feng,Ran Chen,Yiwei Zhang,Naiwen Zhang,Xiaoyu Sang,Qijun Chen
Hypothesis Trypanosomiasis is one of the main threats to human and animal health in African countries. Trypanosoma brucei can evade the host immune recognition by rapidly altering its variant surface glycoprotein (VSG). The ATP synthase F 1 subunit of the parasite exhibits extremely low similarity to that of its mammalian hosts, hypothetically making it an ideal target for the development of novel therapeutics. Experiments Graphene quantum dots (GQDs) were synthesized, and their adhesion to T. brucei surface and internalization was observed microscopically. The activity of ATP synthase and mitochondrial membrane potential of T. brucei were measured after exposure to GQDs. Proteomics, biolayer interferometry, and molecular dynamic simulations were utilized to evaluate the interaction between GQDs with the target proteins. Findings GQDs specifically adhered to the VSG of T. brucei and were conveyed inside the parasite via the VSG internalization pathway. The GQDs promoted intracellular ROS production, interacted with, and inhibited the activity of the p18 subunit of ATP synthase, disrupted parasite mitochondrial membrane potential. Additionally, the GQDs caused a decrease in aminoacyl – tRNA biosynthesis, and upregulated RNA and protein degradation pathways. The findings of this study offer a novel avenue for the target-oriented discovery of anti-trypanosome drugs.
研究领域:
寄生虫学
·
纳米技术
·
分子生物学
·
药物发现
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）