Lysosomal metabolomics reveals V-ATPase- and mTOR-dependent regulation of amino acid efflux from lysosomes
What this study shows
Turns the lysosome from a place where mTORC1 is switched on into something mTORC1 also controls: inhibiting mTOR strongly reduces the efflux of most essential amino acids out of the lysosome, so the organelle becomes a store rather than a source. Measured directly by rapidly isolating lysosomes and profiling their contents, which is why the claim is about concentrations inside the organelle and not inferred from signalling readouts. Boundary: one human cell line, acute pharmacological inhibition.
Abstract
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The lysosome degrades and recycles macromolecules, signals to the cytosol and nucleus, and is implicated in many diseases. Here, we describe a method for the rapid isolation of mammalian lysosomes and use it to quantitatively profile lysosomal metabolites under various cell states. Under nutrient-replete conditions, many lysosomal amino acids are in rapid exchange with those in the cytosol.
Read the full abstract on PubMed →At a glance
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| Evidence type | M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Human cells (HEK293)) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is. |
| Study type | 5 - Mechanistic / In Vitro |
| Model system | Human cells (HEK293) |
| Journal | Science |
| Year | 2017 |
| Peer reviewed | Yes |
| Record last updated | 2026-10-01 |
| Source | DOI 10.1126/science.aan6298 · PMID 29074583 |
Where this study fits
How this study connects to the pathway map, open questions, people and other studies in the Atlas.
Open question
Mechanism-to-outcome gap · H11
When does TBK1 carry the lysosomal-stress signal to TFEB, and when does ULK1?Cited there as evidence. Evidence stands at: Mechanism in cells.
People in the Atlas
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Worked out how to isolate lysosomes fast enough to measure what is inside them, and found that mTOR controls what gets out
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Identified mTOR (as RAFT1) in 1994. His lab then mapped much of the machinery around it: raptor and rictor at the core of mTORC1 and mTORC2, the Rag–Ragulator system that docks mTORC1 on the lysosome, and the sensors that detect leucine, arginine and SAM
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Showed that the lysosomal protein SLC38A9 exports leucine and other essential amino acids out of the lysosome, letting cells grow on proteins they have taken up and broken down there
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Researcher in David Sabatini's lab at the Whitehead Institute who contributed to three studies on how amino acids at the lysosome are sensed by mTORC1
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Cell biologist who helped develop methods to purify intact lysosomes and used them to find what the Batten disease gene CLN3 does, and who now runs a lab at KAUST on lysosome and endoplasmic reticulum defects in rare brain and metabolic diseases
More: 3 other authors
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Researcher at the Whitehead Institute who contributed to studies of lysosome contents, nutrient sensing and cancer metabolism, mostly from David Sabatini's lab
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Chemist and mass-spectrometry specialist at the Whitehead Institute who measured metabolites for many studies of nutrient sensing and cancer metabolism, including the lysosome amino acid work behind two Atlas papers
No profile yet: Abbasi M
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Topics
Extracted findings
These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.
| Intervention | v-ATPase inhibition; mTOR inhibition; nutrient starvation |
| Target | Lysosomal amino-acid efflux, mTOR pathway |
| Model | Human HEK293 cells |
| Effect | Inhibiting mTOR strongly reduced lysosomal efflux of most essential amino acids, converting the lysosome into a depot for them. |
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