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	Ammonia Induces Autophagy through Dopamine Receptor D3 and MTOR
	Li, Zhiyuan1; Ji, Xinmiao1; Wang, Wenchao1; Liu, Juanjuan1,2; Liang, Xiaofei1; Wu, Hong1,2; Liu, Jing1; Eggert, Ulrike S.3,4; Liu, Qingsong1,2; Zhang, Xin1
刊名	PLOS ONE
	2016-04-14
卷号	11期号:4页码:1-24
DOI	10.1371/journal.pone.0153526
文献子类	Article
英文摘要	Hyperammonemia is frequently seen in tumor microenvironments as well as in liver diseases where it can lead to severe brain damage or death. Ammonia induces autophagy, a mechanism that tumor cells may use to protect themselves from external stresses. However, how cells sense ammonia has been unclear. Here we show that culture medium alone containing Glutamine can generate milimolar of ammonia at 37 degrees in the absence of cells. In addition, we reveal that ammonia acts through the G protein-coupled receptor DRD3 (Dopamine receptor D3) to induce autophagy. At the same time, ammonia induces DRD3 degradation, which involves PIK3C3/VPS34-dependent pathways. Ammonia inhibits MTOR (mechanistic target of Rapamycin) activity and localization in cells, which is mediated by DRD3. Therefore, ammonia has dual roles in autophagy: one to induce autophagy through DRD3 and MTOR, the other to increase autophagosomal pH to inhibit autophagic flux. Our study not only adds a new sensing and output pathway for DRD3 that bridges ammonia sensing and autophagy induction, but also provides potential mechanisms for the clinical consequences of hyperammonemia in brain damage, neurodegenerative diseases and tumors.
WOS关键词	PROTEIN-COUPLED RECEPTORS ; LIVER-FAILURE ; HUMAN-DISEASE ; BRAIN ; ANTAGONIST ; INHIBITOR ; CANCER ; ROLES ; CELLS ; HYPERAMMONEMIA
WOS研究方向	Science & Technology - Other Topics
语种	英语
WOS记录号	WOS:000374131700074
资助机构	Chinese Academy of Sciences "Hundred Talent program" ; Chinese Academy of Sciences "Hundred Talent program" ; Chinese Academy of Sciences "Hundred Talent program" ; Chinese Academy of Sciences "Hundred Talent program" ; Chinese Academy of Sciences "Hundred Talent program" ; Chinese Academy of Sciences "Hundred Talent program" ; Chinese Academy of Sciences "Hundred Talent program" ; Chinese Academy of Sciences "Hundred Talent program" ; National Natural Science Foundation of China(31301112) ; National Natural Science Foundation of China(31301112) ; National Natural Science Foundation of China(31301112) ; National Natural Science Foundation of China(31301112) ; National Natural Science Foundation of China(31301112) ; National Natural Science Foundation of China(31301112) ; National Natural Science Foundation of China(31301112) ; National Natural Science Foundation of China(31301112) ; Chinese Academy of Sciences "Hundred Talent program" ; Chinese Academy of Sciences "Hundred Talent program" ; Chinese Academy of Sciences "Hundred Talent program" ; Chinese Academy of Sciences "Hundred Talent program" ; Chinese Academy of Sciences "Hundred Talent program" ; Chinese Academy of Sciences "Hundred Talent program" ; Chinese Academy of Sciences "Hundred Talent program" ; Chinese Academy of Sciences "Hundred Talent program" ; National Natural Science Foundation of China(31301112) ; National Natural Science Foundation of China(31301112) ; National Natural Science Foundation of China(31301112) ; National Natural Science Foundation of China(31301112) ; National Natural Science Foundation of China(31301112) ; National Natural Science Foundation of China(31301112) ; National Natural Science Foundation of China(31301112) ; National Natural Science Foundation of China(31301112)
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/22368]
专题	合肥物质科学研究院_中科院强磁场科学中心
作者单位	1.Chinese Acad Sci, High Field Magnet Lab, Hefei, Anhui, Peoples R China 2.Univ Sci & Technol China, Hefei 230026, Anhui, Peoples R China 3.Kings Coll London, Dept Chem, London WC2R 2LS, England 4.Kings Coll London, Randall Div Cell & Mol Biophys, London WC2R 2LS, England
推荐引用方式 GB/T 7714	Li, Zhiyuan,Ji, Xinmiao,Wang, Wenchao,et al. Ammonia Induces Autophagy through Dopamine Receptor D3 and MTOR[J]. PLOS ONE,2016,11(4):1-24.
APA	Li, Zhiyuan.,Ji, Xinmiao.,Wang, Wenchao.,Liu, Juanjuan.,Liang, Xiaofei.,...&Zhang, Xin.(2016).Ammonia Induces Autophagy through Dopamine Receptor D3 and MTOR.PLOS ONE,11(4),1-24.
MLA	Li, Zhiyuan,et al."Ammonia Induces Autophagy through Dopamine Receptor D3 and MTOR".PLOS ONE 11.4(2016):1-24.

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