Lysosomal nutrients and the mTORC1 pathway

The lysosome is the major catabolic organelle, is the site of activation of the master growth regulator mTORC1 (mechanistic target of rapamycin (mTOR) complex 1), and is often deregulated in common diseases, such as cancer. Given the critical role of lysosomes in maintaining cellular homeostasis, a better understanding of lysosomal function and metabolism and its relation to the mTOR pathway is necessary. Most components of the nutrient-sensing machinery upstream of mTORC1 localize to the lysosomal surface, and amino acids generated by lysosomes regulate mTORC1 by promoting its translocation there, a key step in its activation. Activation of mTORC1 by the amino acid arginine requires SLC38A9, a poorly understood lysosomal membrane protein with homology to amino acid transporters. To study SLC38A9 function at the lysosome, we developed a novel method for the rapid isolation of intact mammalian lysosomes suitable for metabolite profiling.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biology

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2019

Author dc:creator

• Wyant, Gregory A.(Gregory Andrew)

Advisor dc:contributor.advisor

• David M. Sabatini.

• Biology.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/121702

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/121702