Leucine retention in lysosomes is regulated by starvation Journal Article
| Authors: | Bandyopadhyay, U.; Todorova, P.; Pavlova, N. N.; Tada, Y.; Thompson, C. B.; Finley, L. W. S.; Overholtzer, M. |
| Article Title: | Leucine retention in lysosomes is regulated by starvation |
| Abstract: | Cells acquire essential nutrients from the environment and utilize adaptive mechanisms to survive when nutrients are scarce. How nutrients are trafficked and compartmentalized within cells and whether they are stored in response to stress remain poorly understood. Here, we investigate amino acid trafficking and uncover evidence for the lysosomal transit of numerous essential amino acids. We find that starvation induces the lysosomal retention of leucine in a manner requiring RAG-GTPases and the lysosomal protein complex Ragulator, but that this process occurs independently of mechanistic target of rapamycin complex 1 activity. We further find that stored leucine is utilized in protein synthesis and that inhibition of protein synthesis releases lysosomal stores. These findings identify a regulated starvation response that involves the lysosomal storage of leucine. © 2022 National Academy of Sciences. All rights reserved. |
| Keywords: | controlled study; unclassified drug; nonhuman; protein function; animal cell; mouse; enzyme inhibition; embryo; enzyme activity; messenger rna; protein synthesis; western blotting; cell fractionation; upregulation; leucine; mtor; lysosome; guanosine triphosphatase; radiolabeling; male; article; clustered regularly interspaced short palindromic repeat; raga protein; ragb protein |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 119 |
| Issue: | 6 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2022-02-08 |
| Start Page: | e2114912119 |
| Language: | English |
| DOI: | 10.1073/pnas.2114912119 |
| PUBMED: | 35105808 |
| PROVIDER: | scopus |
| PMCID: | PMC8833167 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2022 -- Source: Scopus |
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