Ammonia Induces Autophagy through Dopamine Receptor D3 and MTOR.

Clicks: 255
ID: 59759
2016
Free PDF
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Steady

Ranked #1,307 of 2,056 articles by views in PloS one

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 2,056 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
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.
Reference Key
li2016ammoniaplos Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Li, Zhiyuan;Ji, Xinmiao;Wang, Wenchao;Liu, Juanjuan;Liang, Xiaofei;Wu, Hong;Liu, Jing;Eggert, Ulrike S;Liu, Qingsong;Zhang, Xin;
Journal PloS one
Year 2016
DOI
DOI not found
URL
http://europepmc.org/articles/PMC4831814?pdf=render
Keywords
Medicine (General) Medicine Science cytology physiology

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.