Sit4p is a type 2A-related protein phosphatase in Saccharomyces cerevisiae involved in a wide spectrum of cellular functions, including the glucose repression of mitochondrial transcription. Here we report that Sit4p is also involved in post-translational regulation of mitochondrial proteins and identified 9 potential targets. One of these, the ATP synthase (FoF1 complex) beta subunit Atp2p, was characterized and two phosphorylation sites, T124 and T317, were identified. Expression of Atp2p-T124 or T317 phosphoresistant versions in sit4Δ cells decreased Atp2p phosphorylation confirming these as Sit4p-regulated sites. Moreover, Sit4p and Atp2p interacted both physically and genetically. Mimicking phosphorylation at T124 or T317 increased Atp2p levels, resulting in higher abundance/activity of ATP synthase. Similar changes were observed in sit4Δ cells in which Atp2p is endogenously more phosphorylated. Expression of Atp2-T124 or T317 phosphomimetics also increased mitochondrial respiration and ATP levels and extended yeast lifespan. These results suggest that Sit4p-mediated dephosphorylation of Atp2p-T124/T317 downregulates Atp2p alongside with ATP synthase and mitochondrial function. Combination of transcriptional with post-translational regulation during fermentative growth may allow for a more efficient Sit4p repression of mitochondrial respiration.
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Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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Site | Modification | Modifier | Source | Reference |
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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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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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Evidence ID | Analyze ID | File | Description |
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