Direct control of mitochondrial function by mTOR

被引：266
作者：
Ramanathan, Arvind [1 ]
Schreiber, Stuart L. [1 ]
机构：
[1] Broad Inst, Harvard & Massachusetts Inst Technol, Cambridge Ctr 7, Chem Biol Program, Cambridge, MA 02142 USA
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 52期
关键词：
metabolomics; mitochondria; chemical biology; PATHWAY; BCL-X(L); PROTEIN; FKBP38; INHIBITOR; COMPLEX; GROWTH; VDAC;
D O I：
10.1073/pnas.0912074106
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
mTOR 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.
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收藏
页码：22229 / 22232
页数：4
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