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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.

SUBMITTER: Bandyopadhyay U

PROVIDER: S-EPMC8833167 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Leucine retention in lysosomes is regulated by starvation.

Bandyopadhyay Urmi U Todorova Pavlina P Pavlova Natalya N NN Tada Yuma Y Thompson Craig B CB Finley Lydia W S LWS Overholtzer Michael M

Proceedings of the National Academy of Sciences of the United States of America 20220201 6

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 ...[more]

PMID: 35105808

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