Coordination of mitochondrial bioenergetics with G₁ phase cell cycle progression

Abstract

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 G1 is associated with a significant increase in mitochondrial membrane potential (∆Ψm) and respiration. We used this change in metabolic rate to isolate cells in G1 with low and high levels of mitochondrial membrane potential (∆ΨmL and ∆ΨmH). Biochemical and functional studies demonstrate that ∆ΨmL and ∆ΨmH cells display the distinct characteristics of early and late G1 phase, respectively. We further demonstrate that the metabolic rate in G1 reflect 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 G1 progression and points to the mTOR signaling pathway as a potential molecular coordinator of these two processes.