Coordination of mitochondrial bioenergetics with G1 phase cell cycle progression.
Relatively little is known regarding how energetic demand during cell proliferation is sensed or coordinated with mitochondrial metabolism. Here we demonstrate that cell cycle progression through G(1) is associated with a significant increase in mitochondrial membrane potential (DeltaPsi(m)) and respiration. We used this change in metabolic rate to isolate cells in G(1) with low and high levels of mitochondrial membrane potential (DeltaPsi(m)L and DeltaPsi(m)H). Biochemical and functional studies demonstrate that DeltaPsi(m)L and DeltaPsi(m)H cells display the distinct characteristics of early and late G(1) phase, respectively. We further demonstrate that the metabolic rate in G(1) reflects levels of the mTOR-raptor complex as well as susceptibility to rapamycin-induced cell cycle delay. In conclusion, our data suggests a coupling of mitochondrial bioenergetics and G(1) progression and points to the mTOR signaling pathway as a potential molecular coordinator of these two processes.
Schieke
Stefan M
SM
Translational Medicine Branch, NHLBI, NIH, Bethesda, Maryland 20892-1622, USA.
McCoy
J Philip
JP
Finkel
Toren
T
D048868:Adaptor Proteins, Signal Transducing; D002460:Cell Line; D019069:Cell Respiration; D004734:Energy Metabolism; D016193:G1 Phase; D006801:Humans; D019169:Jurkat Cells; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism*; D011494:Protein Kinases; D011506:Proteins / Q000378:metabolism; D000076223:Regulatory-Associated Protein of mTOR; D058570:TOR Serine-Threonine Kinases
D048868:Adaptor Proteins, Signal Transducing; D011506:Proteins; C463659:RPTOR protein, human; D000076223:Regulatory-Associated Protein of mTOR; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases