Human mitochondrial phosphate/copper carrier SLC25A3

What it acts on

1. SLC25A3 supported copper transport in heterologous assays and reconstituted liposomes.

   Human mitochondrial phosphate/copper carrier SLC25A3 → Copper source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/copper-research/29237729.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1", "start_char": 0, "end_char": 1292, "text_sha256": "d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1"}

   experimental_model

   Carrier perturbation, yeast complementation, bacterial transport and reconstituted liposomes

   exposure

   SLC25A3 loss or reconstitution; extracellular copper addition

   limitations

   The study established copper transport and COX dependence; later export findings extend rather than negate this work. Rescue conditions differ between experiments.

   nutrient_topic

   Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper

   organism

   Human and mouse cells; heterologous yeast and Lactococcus assays

   plain_language

   The mitochondrial phosphate carrier also moves copper.

   primary_references

   [copper-p29237729] The mammalian phosphate carrier SLC25A3 is a mitochondrial copper transporter required for cytochrome c oxidase biogenesis. (2018). https://pubmed.ncbi.nlm.nih.gov/29237729/ DOI: 10.1074/jbc.ra117.000265

   tissue_or_cell_type

   Inner mitochondrial membrane

   transport_effect

   depends Transport supported in heterologous assays and liposomes, with no direction recorded.

   transport_pool

   the mitochondrial matrix Transport supported in heterologous assays and liposomes, with no direction recorded.

   Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 520–531

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Carrier perturbation, yeast complementation, bacterial transport and reconstituted liposomes · source_derived_draft · unverified_draft

   ### copper-slc25a3-copper-carrier SLC25A3 supported copper transport in heterologous assays and reconstituted liposomes. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mitochondrial phosphate carrier also moves copper. organism: Human and mouse cells; heterologous yeast and Lactococcus assays tissue_or_cell_type: Inner mitochondrial membrane experimental_model: Carrier perturbation, yeast complementation, bacterial transport and reconstituted liposomes limitations: The study established copper transport and COX dependence; later export findings extend rather than negate this work. Rescue conditions differ between experiments. exposure: SLC25A3 loss or reconstitution; extracellular copper addition evidence_span: {"source_cache": "artifacts/copper-research/29237729.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1", "start_char": 0, "end_char": 1292, "text_sha256": "d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1"} [copper-p29237729] The mammalian phosphate carrier SLC25A3 is a mitochondrial copper transporter required for cytochrome c oxidase biogenesis. (2018). https://pubmed.ncbi.nlm.nih.gov/29237729/ DOI: 10.1074/jbc.ra117.000265

   Complete structured claim and evidence

2. SLC25A3 knockdown or deletion caused COX deficiency in human and mouse cell models; copper addition suppressed the defects in that study.

   Human mitochondrial phosphate/copper carrier SLC25A3 → Mitochondrial cytochrome c oxidase / respiratory complex IV source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   machinery_impairment Imported condition classification; unverified.

   evidence_span

   {"source_cache": "artifacts/copper-research/29237729.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1", "start_char": 0, "end_char": 1292, "text_sha256": "d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1"}

   experimental_model

   Carrier perturbation, yeast complementation, bacterial transport and reconstituted liposomes

   exposure

   SLC25A3 loss or reconstitution; extracellular copper addition

   limitations

   The study established copper transport and COX dependence; later export findings extend rather than negate this work. Rescue conditions differ between experiments.

   nutrient_topic

   Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper

   organism

   Human and mouse cells; heterologous yeast and Lactococcus assays

   plain_language

   Getting enough copper to the respiratory enzyme depends on transport machinery.

   primary_references

   [copper-p29237729] The mammalian phosphate carrier SLC25A3 is a mitochondrial copper transporter required for cytochrome c oxidase biogenesis. (2018). https://pubmed.ncbi.nlm.nih.gov/29237729/ DOI: 10.1074/jbc.ra117.000265

   tissue_or_cell_type

   Inner mitochondrial membrane

   trigger_kind

   machinery_impairment Imported condition classification; unverified.

   Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 533–544

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Carrier perturbation, yeast complementation, bacterial transport and reconstituted liposomes · source_derived_draft · unverified_draft

   ### copper-slc25a3-cox-deficiency SLC25A3 knockdown or deletion caused COX deficiency in human and mouse cell models; copper addition suppressed the defects in that study. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Getting enough copper to the respiratory enzyme depends on transport machinery. organism: Human and mouse cells; heterologous yeast and Lactococcus assays tissue_or_cell_type: Inner mitochondrial membrane experimental_model: Carrier perturbation, yeast complementation, bacterial transport and reconstituted liposomes limitations: The study established copper transport and COX dependence; later export findings extend rather than negate this work. Rescue conditions differ between experiments. exposure: SLC25A3 loss or reconstitution; extracellular copper addition evidence_span: {"source_cache": "artifacts/copper-research/29237729.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1", "start_char": 0, "end_char": 1292, "text_sha256": "d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1"} [copper-p29237729] The mammalian phosphate carrier SLC25A3 is a mitochondrial copper transporter required for cytochrome c oxidase biogenesis. (2018). https://pubmed.ncbi.nlm.nih.gov/29237729/ DOI: 10.1074/jbc.ra117.000265

   Complete structured claim and evidence

3. Human SLC25A3 expression increased copper export from copper-loaded Lactococcus lactis, supporting an export function.

   Human mitochondrial phosphate/copper carrier SLC25A3 → Copper export across the mitochondrial inner membrane toward the intermembrane space source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/copper-research/42308035.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a172ec9e3d13811a6e6a745d2017398361cc01ec2a06c65065b82ffd06d26d92", "start_char": 0, "end_char": 1276, "text_sha256": "a172ec9e3d13811a6e6a745d2017398361cc01ec2a06c65065b82ffd06d26d92"}

   experimental_model

   Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria

   exposure

   Slc25a3 deletion and elesclomol-copper exposure

   limitations

   Whole-organelle copper was measured, not separate matrix and intermembrane pools. Matrix trapping is the authors mechanism inferred with transport evidence. This recent study complements import findings; bacterial export does not reproduce mitochondrial topology.

   nutrient_topic

   Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper

   organism

   Human protein in Lactococcus lactis

   plain_language

   The carrier can move copper outward as well as support its entry.

   primary_references

   [copper-p42308035] SLC25A3 exports mitochondrial copper to metalate cytochrome c oxidase and prevent cuproptosis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308035/ DOI: 10.1073/pnas.2612098123

   tissue_or_cell_type

   Bacterial assay; mitochondrial export is the linked interpretation

   Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 546–557

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria · source_derived_draft · unverified_draft

   ### copper-slc25a3-export Human SLC25A3 expression increased copper export from copper-loaded Lactococcus lactis, supporting an export function. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The carrier can move copper outward as well as support its entry. organism: Human protein in Lactococcus lactis tissue_or_cell_type: Bacterial assay; mitochondrial export is the linked interpretation experimental_model: Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria limitations: Whole-organelle copper was measured, not separate matrix and intermembrane pools. Matrix trapping is the authors mechanism inferred with transport evidence. This recent study complements import findings; bacterial export does not reproduce mitochondrial topology. exposure: Slc25a3 deletion and elesclomol-copper exposure evidence_span: {"source_cache": "artifacts/copper-research/42308035.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a172ec9e3d13811a6e6a745d2017398361cc01ec2a06c65065b82ffd06d26d92", "start_char": 0, "end_char": 1276, "text_sha256": "a172ec9e3d13811a6e6a745d2017398361cc01ec2a06c65065b82ffd06d26d92"} [copper-p42308035] SLC25A3 exports mitochondrial copper to metalate cytochrome c oxidase and prevent cuproptosis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308035/ DOI: 10.1073/pnas.2612098123

   Complete structured claim and evidence

4. SLC25A3 supplies inorganic phosphate to the mitochondrial matrix for aerobic ATP synthesis; the family study localized the defect to the muscle-expressed isoform.

   Human mitochondrial phosphate/copper carrier SLC25A3 → Inorganic phosphate (Pi; protonation depends on pH) source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/phosphorus-research/17273968.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ff20a374b5c0a96a013cb9dd52c86c9dcc63d157e35e8aac58266dd26da9c0a2", "start_char": 0, "end_char": 805, "text_sha256": "ff20a374b5c0a96a013cb9dd52c86c9dcc63d157e35e8aac58266dd26da9c0a2"}

   experimental_model

   Human family genetics, mitochondrial functional assay and yeast complementation

   exposure

   Two siblings with homozygous SLC25A3 exon-3A c.215G>A, p.Gly72Glu

   limitations

   Isoform- and tissue-specific inherited transport defect; normal dietary phosphorus cannot be assumed to repair the carrier.

   nutrient_topic

   Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus

   organism

   Human; yeast functional complementation

   plain_language

   Phosphate must enter the mitochondrion before it can support ATP production.

   primary_references

   [phosphorus-p17273968] Mitochondrial phosphate-carrier deficiency: a novel disorder of oxidative phosphorylation. (2007). https://pubmed.ncbi.nlm.nih.gov/17273968/ DOI: 10.1086/511788

   tissue_or_cell_type

   Muscle compared with fibroblasts

   transport_effect

   raises Recorded as supplying inorganic phosphate to the matrix.

   transport_pool

   the mitochondrial matrix Recorded as supplying inorganic phosphate to the matrix.

   Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 529–540

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human family genetics, mitochondrial functional assay and yeast complementation · source_derived_draft · unverified_draft

   ### phosphorus-mitochondrial-entry SLC25A3 supplies inorganic phosphate to the mitochondrial matrix for aerobic ATP synthesis; the family study localized the defect to the muscle-expressed isoform. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Phosphate must enter the mitochondrion before it can support ATP production. organism: Human; yeast functional complementation tissue_or_cell_type: Muscle compared with fibroblasts experimental_model: Human family genetics, mitochondrial functional assay and yeast complementation limitations: Isoform- and tissue-specific inherited transport defect; normal dietary phosphorus cannot be assumed to repair the carrier. exposure: Two siblings with homozygous SLC25A3 exon-3A c.215G>A, p.Gly72Glu evidence_span: {"source_cache": "artifacts/phosphorus-research/17273968.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ff20a374b5c0a96a013cb9dd52c86c9dcc63d157e35e8aac58266dd26da9c0a2", "start_char": 0, "end_char": 805, "text_sha256": "ff20a374b5c0a96a013cb9dd52c86c9dcc63d157e35e8aac58266dd26da9c0a2"} [phosphorus-p17273968] Mitochondrial phosphate-carrier deficiency: a novel disorder of oxidative phosphorylation. (2007). https://pubmed.ncbi.nlm.nih.gov/17273968/ DOI: 10.1086/511788

   Complete structured claim and evidence