T. Sekito et al., Mitochondria-to-nuclear signaling is regulated by the subcellular localization of the transcription factors Rtg1p and Rtg3p, MOL BIOL CE, 11(6), 2000, pp. 2103-2115
Cells modulate the expression of nuclear genes in response to changes in th
e functional state of mitochondria, an interorganelle communication pathway
called retrograde regulation. In yeast, expression of the CIT2 gene shows
a typical retrograde response in that its expression is dramatically increa
sed in cells with dysfunctional mitochondria, such as in rho(o) petites. Th
ree genes control this signaling pathway: RTG1 and RTG3, which encode basic
helix-loop-helix leucine zipper transcription factors that bind as heterod
imer to the CIT2 upstream activation site, and RTG2, which encodes a protei
n of unknown function. We show that in respiratory-competent (rho(+)) cells
in which CIT2 expression is low, Rtg1p and Rtg3p exist as a complex largel
y in the cytoplasm, and in rho(o) petites in which CIT2 expression is high,
they exist as a complex predominantly localized in the nucleus. Cytoplasmi
c Rtg3p is multiply phosphorylated and becomes partially dephosphorylated w
hen localized in the nucleus. Rtg2p, which is cytoplasmic in both rho(+) an
d rho(o) cells, is required for the dephosphorylation and nuclear localizat
ion of Rtg3p. Interaction of Rtg3p with Rtg1p is required to retain Rtg3p i
n the cytoplasm of rho(+) cells; in the absence of such interaction, nuclea
r localization and dephosphorylation of Rtg3p is independent of Rtg2p. Our
data show that Rtg1p acts as both a positive and negative regulator of the
retrograde response and that Rtg2p acts to transduce mitochondrial signals
affecting the phosphorylation state and subcellular localization of Rtg3p.