scheggia (sea, CG6782) encodes the Drosophila mitochondrial citrate carrier (DmCIC), the ortholog of human SLC25A1. A member of the mitochondrial carrier family with three SOLCAR repeats, it sits in the inner mitochondrial membrane and exports citrate from the matrix to the cytosol in exchange for malate; reconstituted recombinant Sea shows transport properties similar to mammalian citrate carriers. Cytosolic citrate supplied by Sea is cleaved by ATP-citrate lyase (ATPCL) to acetyl-CoA. sea mutants have impaired mitochondrial citrate efflux, reduced global histone acetylation, extensive chromosome breakage and ATR-dependent cell-cycle arrest in mitotic cells, and Sea is also found in the Nebenkern, the fused mitochondrial derivative of spermatids.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrion, phylogenetic inference. Reason: Mitochondrial carrier family member in the tricarboxylate transport protein subfamily; consistent with experimental localisation. Supporting Evidence: file:DROME/sea/sea-uniprot.txt DR PANTHER; PTHR45788:SF4; TRICARBOXYLATE TRANSPORT PROTEIN, MITOCHONDRIAL; 1. |
| GO:0005739 mitochondrion | IDA PMID:19654186 A conserved role for the mitochondrial citrate transporter S... | ACCEPT | Summary: Mitochondrion, from localisation of Sea (Morciano et al. 2009). Reason: Experimental localisation; Sea is the mitochondrial citrate carrier. Supporting Evidence: PMID:19654186 the Drosophila ortholog of the human mitochondrial citrate carrier Solute carrier 25 A1 (SLC25A1) |
| GO:0006843 mitochondrial citrate transmembrane transport | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrial citrate transmembrane transport, phylogenetic inference. Reason: Core process of the citrate carrier subfamily; supported by fly biochemical and genetic data. Supporting Evidence: PMID:19654186 impair citrate transport from mitochondria to the cytosol |
| GO:0006843 mitochondrial citrate transmembrane transport | IMP PMID:19654186 A conserved role for the mitochondrial citrate transporter S... | ACCEPT | Summary: Mitochondrial citrate transmembrane transport, from sea mutants (Morciano et al. 2009). Reason: sea mutations impair citrate efflux from mitochondria; direct genetic evidence for the core process. Supporting Evidence: PMID:19654186 impair citrate transport from mitochondria to the cytosol |
| GO:0015746 citrate transport | IDA PMID:18515854 Identification of the Drosophila melanogaster mitochondrial ... | MODIFY | Summary: Citrate transport, from reconstitution of recombinant CG6782 in liposomes (Carrisi et al. 2008). Reason: Direct biochemical demonstration of citrate transport by the fly protein; correct, but the more specific mitochondrial citrate transmembrane transport applies, so MODIFY to it, which sea already carries (IBA, IMP). Proposed replacements: mitochondrial citrate transmembrane transport Supporting Evidence: PMID:18515854 It shows to have similar transport properties of the eukaryotic mitochondrial citrate carriers previously biochemically characterized. |
| GO:0016006 Nebenkern | IDA PMID:19654186 A conserved role for the mitochondrial citrate transporter S... | KEEP AS NON CORE | Summary: Nebenkern, from localisation in spermatids (Morciano et al. 2009). Reason: The Nebenkern is the fused mitochondrial derivative of spermatids, so Sea localisation there is expected for a mitochondrial carrier; correct but cell-type-specific. Curators had the full text, which is not in the cache. Supporting Evidence: PMID:19654186 the Drosophila ortholog of the human mitochondrial citrate carrier Solute carrier 25 A1 (SLC25A1) |
| GO:0016020 membrane | IEA GO_REF:0000104 | MODIFY | Summary: Membrane from UniRule. Reason: Correct but very general; Sea is an integral inner mitochondrial membrane protein, so MODIFY to mitochondrial inner membrane (the location used in core_functions; the parent mitochondrial membrane is also annotated). Proposed replacements: mitochondrial inner membrane Supporting Evidence: file:DROME/sea/sea-uniprot.txt DR PROSITE; PS50920; SOLCAR; 3. |
| GO:0031966 mitochondrial membrane | IEA GO_REF:0000044 | MODIFY | Summary: Mitochondrial membrane from UniProt subcellular-location mapping. Reason: Correct but general; mitochondrial carriers reside in the inner membrane, a child of this term, so MODIFY to mitochondrial inner membrane (GO:0005743), as for the membrane row. Support is family membership (curated UniRule mitochondrial carrier family statement; three Solcar repeats) together with the fly study that identified CG6782/Sea by homology to the rat mitochondrial citrate carrier and describes the family as transporting across the inner mitochondrial membrane; that statement is about the carrier family, and the cached abstract does not report a fly membrane-fractionation assay. The record's SUBCELLULAR LOCATION line is an ARBA prediction and is not cited. Proposed replacements: mitochondrial inner membrane Supporting Evidence: file:DROME/sea/sea-uniprot.txt SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family. file:DROME/sea/sea-uniprot.txt Pfam; PF00153; Mito_carr; 3. PMID:18515854 The mitochondrial carriers are a family of transport proteins that shuttle metabolites, nucleotides and cofactors across the inner mitochondrial membrane. |
| GO:0071913 citrate secondary active transmembrane transporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: Citrate secondary active transmembrane transporter activity, phylogenetic inference. Reason: Mitochondrial citrate carriers are citrate/malate exchangers; the fly protein shares the transport properties of characterised citrate carriers. Supporting Evidence: PMID:18515854 It shows to have similar transport properties of the eukaryotic mitochondrial citrate carriers previously biochemically characterized. |
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Download this section (compressed HTML)Q: Does the chromosome breakage of sea mutants arise from reduced histone acetylation, from altered cytosolic lipid synthesis, or from another citrate-dependent process, given that ATPCL loss does not reduce global histone acetylation?
Experiment: Supplement sea mutant larvae with acetate (to bypass citrate via acetyl-CoA synthetase) and score chromosome breaks and histone acetylation.
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Download this section (compressed HTML)scheggia (sea) encodes a carrier protein of the inner mitochondrial membrane that plays a central role in fatty acid and sterol biosynthesis. It catalyses an electroneutral exchange of citrate for another tricarboxylate, a dicarboxylate (L-malate), or phosphoenolpyruvate across the inner mitochondrial membrane. The product of sea is also required to prevent chromosome breaks.
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