Cells modulate the expression of nuclear genes in response to changes in the 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 increased in cells with dysfunctional mitochondria, such as in rho(o) petites. Three genes control this signaling pathway: RTG1 and RTG3, which encode basic helix-loop-helix leucine zipper transcription factors that bind as heterodimer to the CIT2 upstream activation site, and RTG2, which encodes a protein of unknown function. We show that in respiratory-competent (rho(+)) cells in which CIT2 expression is low, Rtg1p and Rtg3p exist as a complex largely in the cytoplasm, and in rho(o) petites in which CIT2 expression is high, they exist as a complex predominantly localized in the nucleus. Cytoplasmic Rtg3p is multiply phosphorylated and becomes partially dephosphorylated when localized in the nucleus. Rtg2p, which is cytoplasmic in both rho(+) and rho(o) cells, is required for the dephosphorylation and nuclear localization of Rtg3p. Interaction of Rtg3p with Rtg1p is required to retain Rtg3p in the cytoplasm of rho(+) cells; in the absence of such interaction, nuclear 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.
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Gene/Complex | Qualifier | Gene Ontology Term | Annotation Extension | Evidence | Source | Assigned On |
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RTG transcription factor complex | located in | nucleus | IDA | ComplexPortal | 2014-10-16 | |
RTG transcription factor complex | involved in | mitochondria-nucleus signaling pathway | IDA | ComplexPortal | 2014-10-16 | |
RTG3 | located in | cytoplasm | IDA | SGD | 2013-08-07 | |
RTG3 | located in | nucleus | IDA | SGD | 2013-08-07 | |
RTG2 | located in | cytoplasm | IDA | SGD | 2013-08-07 | |
RTG2 | involved in | protein localization to nucleus | has input RTG3 | IMP | SGD | 2018-02-08 |
RTG1 | located in | cytoplasm | IDA | SGD | 2013-08-07 | |
RTG1 | located in | nucleus | IDA | SGD | 2013-08-07 |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.