Linking Peroxiredoxin and Vacuolar-ATPase Functions in Calorie Restriction-Mediated Life Span Extension

Figure 1

Model for how CR elicits Tsa1 and Srx1-dependent H₂O₂ resistance and life span extension. (a) At a high concentration of glucose, when increased signaling through both the Ras-Cyr1 and the Gpr1-Gpa2-Cyr1 signaling branches stimulate PKA activity (Box 1), H₂O₂ stress activates Yap1/Skn7-dependent transcription of the SRX1 mRNA but its translation is attenuated by PKA. As a consequence, Srx1 production is diminished and Tsa1 hyper-oxidized and inactivated. (b) During CR, PKA activity is reduced relieving the translational inhibition of the SRX1 mRNA in a Gcn2-dependent manner to provide more Srx1 protein and, as a consequence, more reduced, peroxidase-active Tsa1.

(a)

(b)