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Glucose-mediated mitochondrial reprogramming by cholesterol export at TM4SF5-enriched mitochondria-lysosome contact sites

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Cancer Communications 2024年第1期44卷 47-75页

作者： Ji Eon Kim So-Young Park Chulhwan Kwak Yoonji Lee Dae-Geun Song Jae Woo Jung Haesong Lee Eun-Ae Shin Yangie Pinanga Kyung-hee Pyo Eun Hae Lee Wonsik Kim Soyeon Kim Chang-Duck Jun Jeanho Yun Sun Choi Hyun-Woo Rhee Kwang-Hyeon Liu Jung Weon Lee Department of Pharmacy College of PharmacySeoul National UniversitySeoulRepublic of Korea Research Institute of Pharmaceutical Sciences College of PharmacySeoul National UniversitySeoulRepublic of Korea BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit College of Pharmacy and Research Institute of Pharmaceutical SciencesKyungpook National UniversityDaeguRepublic of Korea Department of Chemistry Seoul National UniversitySeoulRepublic of Korea College of Pharmacy Chung-Ang UniversitySeoulRepublic of Korea Natural Product Informatics Research Center Korea Institute of Science and Technology(KIST)Gangneung-siGangwon-doRepublic of Korea School of Life Sciences Gwangju Institute of Science and Technology(GIST)GwangjuRepublic of Korea Department of Biochemistry College of MedicineDong-A UniversityBusanRepublic of Korea Global AI Drug Discovery Center College of Pharmacy and Graduate School of Pharmaceutical SciencesEwha Womans UniversitySeoulRepublic of Korea Interdisciplinary Program in Genetic Engineering Seoul National UniversitySeoulRepublic of Korea

Background:Transmembrane 4 L six family member 5(TM4SF5)translocates subcellularly and functions metabolically,although it is unclear how intracellu-lar TM4SF5 translocation is linked to metabolic *** is thus of interests to understand how the traffic dynamics of TM4SF5 to subcellular endosomal membranes are correlated to regulatory roles of ***:Here,we explored the metabolic significance of TM4SF5 localization at mitochondria-lysosome contact sites(MLCSs),using in vitro cells and in vivo animal systems,via approaches by immunofluorescence,proximity labelling based proteomics analysis,organelle reconstitution ***:Upon extracellular glucose repletion following depletion,TM4SF5 became enriched at MLCSs via an interaction between mitochondrial FK506-binding protein 8(FKBP8)and lysosomal *** labeling showed molecular clustering of phospho-dynamic-related protein I(DRP1)and certain mitophagy receptors at TM4SF5-enriched MLCSs,leading to mitochondrial fis-sion and ***4SF5 bound NPC intracellular cholesterol transporter 1(NPC1)and free cholesterol,and mediated export of lysosomal cholesterol to mitochondria,leading to impaired oxidative phosphorylation but intact tri-carboxylic acid(TCA)cycle andβ-*** mouse models,hepatocyte Tm4sf5 promoted mitophagy and cholesterol transport to mitochondria,both with positive relations to liver ***:Our findings suggested that TM4SF5-enriched MLCSs regu-late glucose catabolism by facilitating cholesterol export for mitochondrial reprogramming,presumably while hepatocellular carcinogenesis,recapitulating aspects for hepatocellular carcinoma metabolism with mitochondrial repro-gramming to support biomolecule synthesis in addition to glycolytic energetics.

关键词： cholesterol fluorescent imaging glucose catabolism hepatocellular carcinogenesis mem-brane contact sites mitochondria function mitophagy oxidative phosphorylation protein-protein interaction tetraspanin

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植物tetraspanins蛋白的研究进展

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安徽农业科学 2016年第14期44卷 146-148页

作者：赵倩倩王雨欣浙江师范大学化学与生命科学学院浙江金华321004

tetraspanins（TETs）是一大类进化性保守的、具有4次跨膜结构域的蛋白超家族，广泛分布于所有多细胞生物体中。对植物 TETs蛋白的结构特征、系统进化，以及模式植物拟南芥的 TETs 蛋白超家族（AtTET1～17）和番茄 tetraspanin3蛋白的... 详细信息

tetraspanins（TETs）是一大类进化性保守的、具有4次跨膜结构域的蛋白超家族，广泛分布于所有多细胞生物体中。对植物 TETs蛋白的结构特征、系统进化，以及模式植物拟南芥的 TETs 蛋白超家族（AtTET1～17）和番茄 tetraspanin3蛋白的生物功能进行综述，旨在为今后更好地研究植物 TETs 蛋白超家族提供参考。

关键词： 4 次跨膜结构域 AtTET1 ~17 tetraspanin 3 AtTET1-17 tetraspanin3

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Identification,structure and function of a novel tetraspaninhoniologue from Spirometra erinaceieuropaei

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Asian Pacific Journal of Tropical Medicine 2011年第9期4卷 739-742页

作者： Fu Qiongyao Lu Yajun Rao Langyu Chen Jinglong Wu Qiang Cai Qunfang Li Lihua Wu Lixian Lu Gang Department of Clinical Laboratoy Hainan Medicul College Department of Pathogen Biology Hainan Medical College Department of Clinical Biochemistry.Hainan Medical College

Objective:To identify a full length cDNA sequence of a novel tetraspanin(TSP) homologue from Spirometra erinaceieuropaei and to predict the structure and function of its encoding protein using bioinformatics ***:Using the NCBI,EMBI,Expasy and other online sites, the open reading frame(ORF),conserved domain,physical and chemical parameters,signal peptide,transmembrane domain,epitope,topological structures of the protein sequences were *** Vector NTI software was used for multiple sequence alignment and phylogenetic tree ***:’Hie target sequence was 1 132 hp length with a 681 hp biggest ORF encoding 226 amino acids protein with typical TSP conserved *** was confirmed as full length cDNA of TSP16 from Spirometra erinaceieuropaei and named as SeTSP16 (GenBank accession number:JF728872).The predicted molecular weight and isoelectric point of the deduced protein were 24 750.5 Da and 7.88 Da,*** with TSP16s from Schistosoma japonicum and Schistosoma *** showed similarity of 59%and 59%, ***16 contained four transmembrane domains(TM 1-4),intracellular N and C-termini,one short small extracellular loop and one large extracellular *** major epitopes that were significant different from the corresponding epitope regions of TSP16 from Schistosoma mansoni and Schistosoma japonicum were ***:The full length cDNA sequences of SeTSP16 arc *** encodes a transmembrane protein which might be an ideal diagnosis antigen and target molecule for antiparasitic drugs.

关键词： Spirometra erinaceieuropaei tetraspanin Prediction Structure Function

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Novel CD9-targeted therapies in gastric cancer

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World Journal of Gastroenterology 2015年第11期21卷 3206-3213页

作者： Yoko Murayama Kenji Oritani Shusaku Tsutsui Department of Gastro-enterology and Hepatology Itami City Hospital Department of Hematology/Oncology Graduate School of MedicineOsaka University

There are 33 human tetraspanin proteins,emerging as key players in malignancy,the immune system,fertilization,cellular signaling,adhesion,morphology,motility,proliferation,and tumor ***9,a member of the tetraspanin family,associates with and influences a variety of cell-surface *** these interactions,CD9 modifies multiple cellular events,including adhesion,migration,proliferation,and ***9 is therefore considered to play a role in several stages during cancer *** CD9 expression is generally related to venous vessel invasion and metastasis as well as poor *** found that treatment of mice bearing human gastric cancer cells with anti-CD9 antibody successfully inhibited tumor progression via antiproliferative,proapoptotic,and antiangiogenic effects,strongly indicating that CD9 is a possible therapeutic target in patients with gastric ***,we describe the possibility of CD9 manipulation as a novel therapeutic strategy in gastric cancer,which still shows poor prognosis.

关键词： CD9 tetraspanin Gastric cancer Tumo-rigenicity The

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血吸虫疫苗研究新进展

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国际生物制品学杂志 2007年第6期30卷 267-271页

作者：付译节陈建平杨莉四川大学华西医院肿瘤生物治疗国家重点实验室成都610041 四川大学华西基础医学与法医学院寄生虫教研室

血吸虫病是一种防治难度极大的人畜共患寄生虫病,在全球范围内其患病人数仅次于疟疾,是第二大热带寄生虫病。数十年来,血吸虫疫苗研究逐步从死疫苗、减毒活疫苗发展到基因工程亚单位疫苗。随着血吸虫分子生物学领域的飞速发展,血吸虫基... 详细信息

血吸虫病是一种防治难度极大的人畜共患寄生虫病,在全球范围内其患病人数仅次于疟疾,是第二大热带寄生虫病。数十年来,血吸虫疫苗研究逐步从死疫苗、减毒活疫苗发展到基因工程亚单位疫苗。随着血吸虫分子生物学领域的飞速发展,血吸虫基因组学、转录组学和大部分蛋白组学研究基本完成,人们发现了一批新的疫苗候选分子。本文综述了血吸虫疫苗新近的研究进展,着重描述了tetraspanin 为代表的膜蛋白疫苗。

关键词：血吸虫病疫苗膜蛋白 tetraspanin

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