Lysosomal metabolomics reveals V-ATPase- and mTOR-dependent regulation of amino acid efflux from lysosomes
Broad Institute · Howard Hughes Medical Institute · +3 more institutions
Abstract
-adenosine triphosphatase (V-ATPase) increased the luminal concentrations of most metabolites but had no effect on those of the majority of essential amino acids. Instead, nutrient starvation regulates the lysosomal concentrations of these amino acids, an effect we traced to regulation of the mechanistic target of rapamycin (mTOR) pathway. Inhibition of mTOR strongly reduced the lysosomal efflux of most essential amino acids, converting the lysosome into a cellular depot for them. These results reveal the dynamic nature of lysosomal metabolites and that V-ATPase- and mTOR-dependent mechanisms exist for controlling lysosomal amino acid efflux.
Citation impact
- FWCI
- 29.71
- Percentile
- 100%
- References
- 48
Authors
8- MAMonther Abu-RemailehCorresponding
Broad Institute, Howard Hughes Medical Institute, Allen Institute, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology
- GAGregory A. WyantCorresponding
Broad Institute, Howard Hughes Medical Institute, Allen Institute, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology
- CKChoah Kim
Broad Institute, Howard Hughes Medical Institute, Allen Institute, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology
- NNNouf N. Laqtom
Broad Institute, Howard Hughes Medical Institute, Allen Institute, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology
- MAMaria Abbasi
Broad Institute, Howard Hughes Medical Institute, Allen Institute, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology
Topics & keywords
- Lysosome
- Cytosol
- Amino acid
- Biochemistry
- PI3K/AKT/mTOR pathway
- ATPase
- Biology
- V-ATPase
- Clean water and sanitation