論文 - 詳細
| RRC ID | 62311 |
|---|---|
| 著者 | Wilden AR, Molina JA, Feuerborn M, Boyle D, Lee SY. |
| タイトル | Glutamine-dependent lysosome homeostatic changes induced by starvation and lysosome inhibition. |
| ジャーナル | Biochim Biophys Acta Mol Cell Res |
| Abstract |
Lysosomes are a major organelle for degrading macromolecules. When deprived of nutrients, cells activate the autophagy and lysosome biogenesis pathways to recycle cytoplasmic materials and to increase lysosomal degradation capacity for survival, respectively. We have identified a condition in which cells accumulated enlarged lysosomes upon starvation and lysosome inhibition. Selective autophagy and inhibition of the mechanistic target of rapamycin (mTOR) in combination with lysosome inhibition were not able to induce this phenomenon. Conversely, knocking out autophagy genes, ATG5 or ATG7, had no effects on the enlarged lysosome formation. This suggests that the enlarged lysosome formation is an autophagy independent process. Remarkably, adding glutamine to the treatment can prevent formation of the enlarged lysosomes and dissipate the pre-existing ones. Furthermore, the nucleus/cytoplasm translocation of the transcription factor EB (TFEB), but not mTOR activity, correlates with the formation/dissipation of enlarged lysosomes. Knockdown of TFEB, however, suggests that TFEB-mediated lysosome biogenesis is not directly involved in the process. These results indicate that there is a novel mechanism by which lysosome homeostasis can be regulated under certain stress conditions. |
| 巻・号 | 1865(9) |
| ページ | 1356-1367 |
| 公開日 | 2018-9-1 |
| DOI | 10.1016/j.bbamcr.2018.06.014 |
| PII | S0167-4889(18)30144-7 |
| PMID | 29966622 |
| PMC | PMC6392085 |
| MeSH | Animals Autophagy Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism* Cell Line Glutamine / drug effects* HeLa Cells Homeostasis Humans Lysosomes / physiology* Mice TOR Serine-Threonine Kinases / antagonists & inhibitors TOR Serine-Threonine Kinases / metabolism* |
| IF | 4.105 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Atg5^(+/+)MEF(RCB2710) Atg5^(-/-)MEF(RCB2711) Atg7 +/+ MEFs(RCB3706) Atg7 -/- MEFs(RCB3707) |