Ammonia Induces Autophagy through Dopamine Receptor D3 and MTOR

doi:10.1371/journal.pone.0153526

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	Ammonia Induces Autophagy through Dopamine Receptor D3 and MTOR
	Li, Zhiyuan1 ; Ji, Xinmiao 1; Wang, Wenchao1 ; Liu, Juanjuan1,2 ; Liang, Xiaofei 1; Wu, Hong1,2 ; Liu, Jing 1; Eggert, Ulrike S.3,4; Liu, Qingsong1,2 ; Zhang, Xin1
	2016-04-14
发表期刊	PLOS ONE
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.
文章类型	Article
WOS标题词	Science & Technology
DOI	10.1371/journal.pone.0153526
关键词[WOS]	PROTEIN-COUPLED RECEPTORS ; LIVER-FAILURE ; HUMAN-DISEASE ; BRAIN ; ANTAGONIST ; INHIBITOR ; CANCER ; ROLES ; CELLS ; HYPERAMMONEMIA
收录类别	SCI
语种	英语
项目资助者	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)
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000374131700074
引用统计	被引频次：23[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.hfcas.ac.cn:8080/handle/334002/22368
专题	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
第一作者单位	中科院强磁场科学中心
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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