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NQR1 controls lifespan by regulating the promotion of respiratory metabolism in yeast

2009; Wiley; Volume: 8; Issue: 2 Linguagem: Inglês

10.1111/j.1474-9726.2009.00461.x

1474-9726

María Jiménez‐Hidalgo, Carlos Santos–Ocaña, Sergio Padilla, José M. Villalba, Guillermo López‐Lluch, Alejandro Martín‐Montalvo, Robin K. Minor, David Sinclair, Rafael de Cabo, Plácido Navas,

Biochemical Acid Research Studies

The activity and expression of plasma membrane NADH coenzyme Q reductase is increased by calorie restriction (CR) in rodents. Although this effect is well-established and is necessary for CR's ability to delay aging, the mechanism is unknown. Here we show that the Saccharomyces cerevisiae homolog, NADH-Coenzyme Q reductase 1 (NQR1), resides at the plasma membrane and when overexpressed extends both replicative and chronological lifespan. We show that NQR1 extends replicative lifespan in a SIR2-dependent manner by shifting cells towards respiratory metabolism. Chronological lifespan extension, in contrast, occurs via an SIR2-independent decrease in ethanol production. We conclude that NQR1 is a key mediator of lifespan extension by CR through its effects on yeast metabolism and discuss how these findings could suggest a function for this protein in lifespan extension in mammals.