Figure 8.

Model of the control of mitochondria-to-nuclear signaling. In cells with dysfunctional mitochondria, one or more signals, one of which is possibly the level of glutamate produced from the TCA cycle, are transmitted from mitochondria (bold, dashed arrow) via Rtg2p to a cytoplasmic complex between Rtg1p and a highly phosphorylated form of Rtg3p. This complex, which may include other factors not indicated, becomes transiently dissociated along with a dephosphorylation of Rtg3p. Rtg1p and Rtg3p then translocate to the nucleus and assemble for transcriptional activation at target gene R box sites, GTCAC. The phosphorylation state of cytoplasmic Rtg3p is sensitive to a feedback response, indicated by the light green arrow, in that the absence of Rtg1p–Rtg3p-dependent transcription in the nucleus activates further dephosphorylation and nuclear translocation of cytoplasmic Rtg3p. It is not known whether dephosphorylation of cytoplasmic Rtg3p is caused by inactivation of a kinase or activation of a phosphatase.