The mechanistic target of rapamycin (mTOR) signaling pathway senses and integrates a variety of environmental cues to regulate organismal growth and homeostasis. The pathway regulates many major cellular processes and is implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes, and neurodegeneration. Here, we review recent advances in our understanding of the mTOR pathway and its role in health, disease, and aging. We further discuss pharmacological approaches to treat human pathologies linked to mTOR deregulation.

mTOR Signaling in Growth Control and Disease

mTOR signaling in growth control and disease.

https://archive-ouverte.unige.ch/unige:18229/ATTACHMENT01

TOR signaling in growth and metabolism.

In certain aspects, the invention relates to methods for identifying compounds which modulate Akt activity mediated by the rictor-mTOR complex and methods for treating or preventing a disorder that is associated with aberrant Akt activity.

http://science.sciencemag.org/content/sci/307/5712/1098.full.pdf

Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex

mTOR Signaling in Growth, Metabolism, and Disease.

Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control

http://www.mcb5068.wustl.edu/MCB/DiscussionSection/PDF_Files/mTORC2.pdf

Activation of mTORC2 by Association with the Ribosome

https://www.cell.com/molecular-cell/pdf/S1097-2765(12)00488-1.pdf

Glutaminolysis activates Rag-mTORC1 signaling

Molecular Organization of Target of Rapamycin Complex 2

Yeast cytochrome c oxidase subunit IV (an imported mitochondrial protein) is made as a larger precursor with a transient pre-sequence of 25 amino acids. If this pre-sequence is fused to the amino terminus of mouse dihydrofolate reductase (a cytosolic protein) the resulting fusion protein is imported into the matrix space, and cleaved to a smaller size, by isolated yeast mitochondria. We have now fused progressively shorter amino-terminal segments of the subunit IV pre-sequence to dihydrofolate reductase and tested each fusion protein for import into the matrix space and cleavage by the matrix-located processing protease. The first 12 amino acids of the subunit IV pre-sequence were sufficient to direct dihydrofolate reductase into the mitochondrial matrix, both in vitro and in vivo. However, import of the corresponding fusion protein into the matrix was no longer accompanied by proteolytic processing. Fusion proteins containing fewer than nine amino-terminal residues from the subunit IV pre-piece were not imported into isolated mitochondria. The information for transporting attached mouse dihydrofolate reductase into mitochondria is thus contained within the first 12 amino acids of the subunit IV pre-sequence.

The first twelve amino acids (less than half of the pre-sequence) of an imported mitochondrial protein can direct mouse cytosolic dihydrofolate reductase into the yeast mitochondrial matrix.

Wolfgang Oppliger

Papers

Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control

Activation of mTORC2 by Association with the Ribosome

Glutaminolysis activates Rag-mTORC1 signaling

Molecular Organization of Target of Rapamycin Complex 2

The first twelve amino acids (less than half of the pre-sequence) of an imported mitochondrial protein can direct mouse cytosolic dihydrofolate reductase into the yeast mitochondrial matrix.