Scientific Publications

Direct control of mitochondrial function by mTOR.

Publication TypeJournal Article
AuthorsRamanathan, A., and Schreiber SL
AbstractmTOR is a central regulator of cellular growth and metabolism. Using metabolic profiling and numerous small-molecule probes, we investigated whether mTOR affects immediate control over cellular metabolism by posttranslational mechanisms. Inhibiting the FKBP12/rapamycin-sensitive subset of mTOR functions in leukemic cells enhanced aerobic glycolysis and decreased uncoupled mitochondrial respiration within 25 min. mTOR is in a complex with the mitochondrial outer-membrane protein Bcl-xl and VDAC1. Bcl-xl, but not VDAC1, is a kinase substrate for mTOR in vitro, and mTOR regulates the association of Bcl-xl with mTOR. Inhibition of mTOR not only enhances aerobic glycolysis, but also induces a state of increased dependence on aerobic glycolysis in leukemic cells, as shown by the synergy between the glycolytic inhibitor 2-deoxyglucose and rapamycin in decreasing cell viability.
Year of Publication2009
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue52
Pages22229-32
Date Published (YYYY/MM/DD)2009/12/29
ISSN Number0027-8424
DOI10.1073/pnas.0912074106
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/20080789?dopt=Abstract