Please wait a minute...
浙江大学学报(医学版)  2016, Vol. 45 Issue (3): 308-314    DOI: 10.3785/j.issn.1008-9292.2019.05.15
刘巧云1, 沈汉明2, 夏大静1
1. 浙江大学公共卫生学院毒理系, 浙江 杭州 310058;
2. 新加坡国立大学杨潞龄医学院生理系, 117597
Zinc and autophagy
LIU Qiaoyun1, SHEN Hanming2, XIA Dajing1
1. Department of Toxicology, School of Public Health, Zhejiang University, Hangzhou 310058, China;
2. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore
全文: PDF(979 KB)  


关键词 自噬肿瘤综述    

Autophagy refers to a catabolic process,in which the damaged organelles or biological macromolecules, such as protein aggregates, are degraded via lysosome. The completion of autophagy depends on a series of autophagy-related genes (Atgs) and many upstream regulatory molecules. Zinc is an essential trace element, and plays an important role in the process of autophagy as a component of enzymes and structural proteins like zinc transporters or zinc finger protein. The regulation of autophagy is closely associated with the zinc ion homeostasis. In addition, many studies suggest that the protective effects of zinc on cells are likely to be done by autophagy. This review aims to summarize the current research progress and discuss the reciprocal regulation mechanism between zinc and autophagy, which may provide insights into the intricate roles of autophagy in diseases and find novel strategies for treatment and prevention of human diseases.

Key wordsZinc    Autophagy    Neoplasms    Review
收稿日期: 2015-10-19
CLC:  R225  


通讯作者: 夏大静(1968-),女,博士,教授,主要从事免疫毒理学研究;;     E-mail:
作者简介: 刘巧云(1992-),女,硕士研究生,主要从事农药毒理学研究;;
E-mail Alert


刘巧云 等. 锌与自噬[J]. 浙江大学学报(医学版), 2016, 45(3): 308-314.
LIU Qiaoyun, SHEN Hanming, XIA Dajing. Zinc and autophagy. Journal of ZheJiang University(Medical Science), 2016, 45(3): 308-314.

链接本文:      或

[1] MIZUSHIMA N, LEVINE B, CUERVO A M, et al. Autophagy fights disease through cellular self-digestion[J]. Nature, 2008, 451(7182):1069-1075.
[2] MIZUSHIMA N, LEVINE B. Autophagy in mammalian development and differentiation[J]. Nat Cell Biol, 2010, 12(9): 823-830.
[3] HIRANO T, MURAKAMI M, FUKADA T, et al. Roles of zinc and zinc signaling in immunity: zinc as an intracellular signaling molecule[J]. Adv Immunol, 2008, 97: 149-176.
[4] LIUZZI J P, GUO L, YOO C, et al. Zinc and autophagy[J]. Biometals, 2014, 27(6): 1087-1096.
[5] ZHAO Z, FUX B, GOODWIN M, et al. Autophagosome-independent essential function for the autophagy protein Atg5 in cellular immunity to intracellular pathogens[J]. Cell Host Microbe, 2008, 4(5): 458-469.
[6] YANG Z, KLIONSKY D J. Eaten alive: a history of macroautophagy[J]. Nat Cell Biol, 2010, 12(9): 814-822.
[7] JUNG C H, RO S H, CAO J, et al. mTOR regulation of autophagy[J]. FEBS Lett, 2010, 584(7):1287-1295.
[8] REGGIORI F,SHINTANI T,NAIR U, et al. Atg9 cycles between mitochondria and the pre-autophagosomal structure in yeasts[J]. Autophagy, 2005, 1(2):101-109.
[9] ITAKURA E, MIZUSHIMA N. Characterization of autophagosome formation site by a hierarchical analysis of mammalian Atg proteins[J]. Autophagy, 2010, 6(6): 764-776.
[10] JUNG C H, JUN C B, RO S H, et al. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery[J]. Mol Biol Cell, 2009, 20(7): 1992-2003.
[11] MIZUSHIMA N, KUMA A, KOBAYASHI Y, et al. Mouse Apg16L, a novel WD-repeat protein, targets to the autophagic isolation membrane with the Apg12-Apg5 conjugate[J]. J Cell Sci, 2003, 116(Pt 9): 1679-1688.
[12] YU X, LONG Y C, SHEN H M. Differential regulatory functions of three classes of phosphatidylinositol and phosphoinositide 3-kinases in autophagy[J]. Autophagy, 2015, 11(10):1711-1728.
[13] HE R, PENG J, YUAN P, et al. Divergent roles of BECN1 in LC3 lipidation and autophagosomal function[J]. Autophagy, 2015, 11(5): 740-747.
[14] IN S, HONG C W, CHOI B, et al. Inhibition of mitochondrial clearance and Cu/Zn-SOD activity enhance 6-hydroxydopamine-induced neuronal apoptosis[J]. Mol Neurobiol, 2016, 53(1):777-791.
[15] PAN R, TIMMINS G S, LIU W, et al. Autophagy mediates astrocyte death during zinc-potentiated ischimia-reperfusion injury[J]. Biol Trace Elem Res, 2015, 166(1): 89-95.
[16] LIUZZI J P, YOO C. Role of zinc in the regulation of autophagy during ethanol exposure in human hepatoma cells[J]. Biol Trace Elem Res, 2013, 156(1-3): 350-356.
[17] HWANG J J, KIM H N, KIM J, et al. Zinc(Ⅱ) ion mediates tamoxifen-induced autophagy and cell death in MCF-7 breast cancer cell line[J]. Biometals, 2010, 23(6): 997-1013.
[18] ALAM S, KELLEHER S L. Cellular mechanisms of zinc dysregulation: a perspective on zinc homeostasis as an etiological factor in the development and progression of breast cancer[J]. Nutrients, 2012, 4(8): 875-903.
[19] LI Y, ZHANG L, LI K, et al. ZNF32 inhibits autophagy through the mTOR pathway and protects MCF-7 cells from stimulus-induced cell death[J]. Sci Rep, 2015, 5: 9288.
[20] HUNG H H, HUANG W P, PAN C Y. Dopamine-and zinc-induced autophagosome formation facilitates PC12 cell survival[J]. Cell Biol Toxicol, 2013, 29(6): 415-429.
[21] SEO B R, LEE S J, CHO K S, et al. The zinc ionophore clioquinol reverses autophagy arrest in chloroquine-treated ARPE-19 cells and in APP/mutant presenilin-1-transfected Chinese hamster ovary cells[J]. Neurobiol Aging, 2015, 36(12):3228-3238.
[22] KIM J, KUNDU M, VIOLLET B, et al. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1[J]. Nat Cell Biol, 2011,13(2): 132-141.
[23] LEE S J, KOH J Y. Roles of zinc and metallothionein-3 in oxidative stress-induced lysosomal dysfunction, cell death, and autophagy in neurons and astrocytes[J]. Mol Brain, 2010,3(1): 30.
[24] LICHTLEN P, SCHAFFNER W. The "metal transcription factor" MTF-1: biological facts and medical implications[J]. Swiss Med Wkly, 2002, 131(45-46): 647-652.
[25] CARTHARIUS K, FRECH K, GROTE K, et al. MatInspector and beyond: promoter analysis based on transcription factor binding sites[J]. Bioinformatics, 2005, 21(13): 2933-2942.
[26] KIM J H, JEON J, SHIN M, et al. Regulation of the catabolic cascade in osteoarthritis by the zinc-ZIP8-MTF1 axis[J]. Cell, 2014, 156(4): 730-743.
[27] RYU M S, LANGKAMP-HENKEN B, CHANG S M, et al. Genomic analysis, cytokine expression, and microRNA profiling reveal biomarkers of human dietary zinc depletion and homeostasis[J]. Proc Natl Acad Sci U S A, 2011, 108(52): 20970-20975.
[28] ENG B H, GUERIONT M L, EIDE D, et al. Sequence analyses and phylogenetic characterization of the ZIP family of metal ion transport proteins[J]. J Membr Biol, 1998, 166(1): 1-7.
[29] PATRUSHEV N, SEIDEL-ROGOL B, SALAZAR G. Angiotensin Ⅱ requires zinc and downregulation of the zinc transporters ZnT3 and ZnT10 to induce senescence of vascular smooth muscle cells[J/OL]. PLoS One, 2012, 7(3):e33211.
[30] BOSOMWORTH H J, ADLARD P A, FORD D, et al. Altered expression of ZnT10 in Alzheimer's disease brain[J/OL]. PLoS One, 2013, 8(5):e65475.
[31] KAMBE T. An overview of a wide range of functions of ZnT and Zip zinc transporters in the secretory pathway[J]. Biosci Biotechnol Biochem, 2011, 75(6): 1036-1043.
[32] KUMA A, MIZUSHIMA N, ISHIHARA N, et al. Formation of the approximately 350-kDa Apg12-Apg5.Apg16 multimeric complex, mediated by Apg16 oligomerization, is essential for autophagy in yeast[J]. J Biol Chem, 2002, 277(21): 18619-18625.
[33] DING W X, LI M, CHEN X, et al. Autophagy reduces acute ethanol-induced hepatotoxicity and steatosis in mice[J]. Gastroenterology, 2010, 139(5): 1740-1752.
[34] DERETIC V, SAITOH T, AKIRA S. Autophagy in infection, inflammation and immunity[J]. Nat Rev Immunol, 2013, 13(10): 722-737.
[35] MANLEY S, WILLIAMS J A, DING W X. Role of p62/SQSTM1 in liver physiology and pathogenesis[J]. Exp Biol Med (Maywood), 2013, 238(5): 525-538.
[36] Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls[J]. Nature, 2007, 447(7145): 661-678.
[37] TAYLOR K M, VICHOVA P, JORDAN N, et al. ZIP7-mediated intracellular zinc transport contributes to aberrant growth factor signaling in antihormone-resistant breast cancer cells[J]. Endocrinology, 2008, 149(10): 4912-4920.
[38] SUMMERSGILL H, ENGLAND H, LOPEZ-CASTEJON G, et al. Zinc depletion regulates the processing and secretion of IL-1β[J/OL]. Cell Death Dis, 2014, 5(1):e1040.
[1] 蔡成,王建平,钟志凤,戴志慧,王庆华,董武真,施红旗,刘庆伟,杜金林. 缺氧诱导因子1α和CD133预测直肠癌患者新辅助放化疗疗效的临床研究[J]. 浙江大学学报(医学版), 2017, 46(1): 36-43.
[2] 陈刚,张鼎,应亚草,王志峰,陶伟,朱皓,张景峰,彭志毅. 国产载药微球经动脉化疗栓塞治疗不可切除原发性肝癌的临床研究[J]. 浙江大学学报(医学版), 2017, 46(1): 44-51.
[3] 郑艳榕,张翔南,陈忠. Nix介导的线粒体自噬机制的研究进展[J]. 浙江大学学报(医学版), 2017, 46(1): 92-96.
[4] 李文龙,瞿海斌. 近红外光谱应用于中药质量控制及生产过程监控的研究进展[J]. 浙江大学学报(医学版), 2017, 46(1): 80-88.
[5] 高思倩,沈咏梅,耿福能,李艳华,高建青. 糖尿病溃疡动物模型的建立及相关治疗研究进展[J]. 浙江大学学报(医学版), 2017, 46(1): 97-105.
[6] 王颖,汪仪,陈忠. 中枢胆碱能系统与癫痫关系的研究进展[J]. 浙江大学学报(医学版), 2017, 46(1): 15-21.
[7] 高思倩,沈咏梅,耿福能,李艳华,高建青. 颞叶癫痫与海马成体神经再生[J]. 浙江大学学报(医学版), 2017, 46(1): 97-105.
[8] 封盛 等. 糖皮质激素受体信号通路在膀胱癌治疗中的作用研究进展[J]. 浙江大学学报(医学版), 2016, 45(6): 655-660.
[9] 李统宇 等. 杜氏肌营养不良疾病模型及基因治疗研究进展[J]. 浙江大学学报(医学版), 2016, 45(6): 648-654.
[10] 夏光发 等. 新辅助化疗前后激素受体变化的乳腺癌患者辅助内分泌治疗的疗效[J]. 浙江大学学报(医学版), 2016, 45(6): 614-619.
[11] 曹鹏 等. 双氢青蒿素抗肿瘤分子生物学机制研究进展[J]. 浙江大学学报(医学版), 2016, 45(5): 501-507.
[12] 李亭亭 等. 中性粒细胞在哮喘中作用的研究进展[J]. 浙江大学学报(医学版), 2016, 45(5): 544-549.
[13] 王雪 等. TANK结合激酶1在抗病毒免疫应答中的作用研究进展[J]. 浙江大学学报(医学版), 2016, 45(5): 550-557.
[14] 杜苗苗 等. 钙化性主动脉瓣疾病药物治疗研究进展[J]. 浙江大学学报(医学版), 2016, 45(4): 432-438.
[15] 郑江江 等. 肿瘤相关成纤维细胞CD10表达在结直肠腺瘤癌变和复发中的意义[J]. 浙江大学学报(医学版), 2016, 45(4): 335-341.