Fumarase and aconitase in yeast are dual localized to the cytosol and mitochondria by a similar targeting mechanism. These two tricarboxylic acid cycle enzymes are single translation products that are targeted to and processed by mitochondrial processing peptidase in mitochondria prior to distribution. The mechanism includes reverse translocation of a subset of processed molecules back into the cytosol. Here, we show that either depletion or overexpression of Cit2 (cytosolic citrate synthase) causes the vast majority of fumarase to be fully imported into mitochondria with a tiny amount or no fumarase in the cytosol. Normal dual distribution of fumarase (similar amounts in the cytosol and mitochondria) depends on an enzymatically active Cit2. Glyoxylate shunt deletion mutations (Deltamls1, Deltaaco1 and Deltaicl1) exhibit an altered fumarase dual distribution (like in Deltacit2). Finally, when succinic acid, a product of the glyoxylate shunt, is added to the growth medium, fumarase dual distribution is altered such that there are lower levels of fumarase in the cytosol. This study suggests that the cytosolic localization of a distributed mitochondrial protein is governed by intracellular metabolite cues. Specifically, we suggest that metabolites of the glyoxylate shunt act as 'nanosensors' for fumarase subcellular targeting and distribution. The possible mechanisms involved are discussed.
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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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