Affinage

COX17

Cytochrome c oxidase copper chaperone · UniProt Q14061

Length
63 aa
Mass
6.9 kDa
Annotated
2026-06-09
39 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COX17 is a mitochondrial intermembrane space (IMS) copper chaperone that delivers copper to the cytochrome c oxidase (complex IV) assembly machinery, a role first established genetically when a cox17 null mutant was shown to be specifically rescued by copper supplementation (PMID:8662933) and confirmed to be functionally conserved in humans by complementation of the yeast mutant (PMID:9050918). The protein is imported into the IMS in an unstructured, fully reduced state and trapped there by Mia40-dependent oxidation to the Cox17²ˢ⁻ˢ form, which acquires a coiled-coil-helix fold stabilized by two disulfide bonds and binds a single Cu(I) ion through a Cys-Cys motif (PMID:18093982, PMID:15893662). Its redox-dependent metal-binding repertoire is graded across oxidation states: fully reduced Cox17 binds up to four Cu(I) ions in a polycopper Cu₄S₆ cluster, the doubly-disulfide form binds one Cu(I), and the fully oxidized form binds none (PMID:17672825, PMID:15142040, PMID:15893662). A C-terminal amphipathic helix retains Cox17 in the IMS, and tethering it to the inner membrane fully restores function, demonstrating that its activity is confined to this compartment (PMID:14615477). The metallated Cox17²ˢ⁻ˢ form directly and specifically transfers Cu(I) to both Sco1 and Cox11 in vitro, feeding the Cu_A and Cu_B sites of complex IV; transfer to Sco1 is mechanistically coupled to a two-electron transfer that oxidizes Cox17 to its disulfide form, and the C57Y mutant selectively loses the Sco1 pathway while retaining transfer to Cox11 (PMID:15199057, PMID:18458339). Disruption of COX17 in human cells reduces intramitochondrial copper, impairs complex IV assembly with accumulation of subassemblies lacking copper-loaded Cox2, and alters mitochondrial cristae ultrastructure (PMID:19393246, PMID:31903891). The chaperone's activity is positively regulated by MOF-KANSL-mediated acetylation (PMID:37813994), and it interacts with the MICOS component Mic60 to modulate inner-membrane architecture in a copper-regulated manner (PMID:25918166). A patient SCO1 P174L mutation that blocks Cox17-mediated metallation of Sco1 establishes the clinical relevance of this transfer step to complex IV deficiency (PMID:16520371). Beyond copper handling, Cox17 binds cisplatin at its Cu(I)-coordinating cysteines and facilitates platinum delivery to mitochondria (PMID:27539433, PMID:26399480).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 1996 High

    Established that COX17 is dedicated to copper delivery for complex IV assembly rather than general copper metabolism, defining the gene's biological purpose.

    Evidence Genetic complementation and copper-supplementation rescue of a yeast cox17 null mutant

    PMID:8662933

    Open questions at the time
    • Did not localize the protein or identify the molecular form of copper delivered
    • Downstream acceptors of copper not yet identified
  2. 1997 High

    Showed the copper-delivery mechanism is conserved to humans, validating yeast as a model for the human chaperone.

    Evidence Functional complementation of yeast cox17 null with human cDNA

    PMID:9050918

    Open questions at the time
    • Did not characterize human protein structure or partners
    • Conservation of mechanism inferred from rescue, not directly demonstrated biochemically
  3. 1998 High

    Defined the chemical nature of copper binding, distinguishing a labile delivery-competent cluster from stable storage proteins.

    Evidence EXAFS and UV-vis/emission spectroscopy of the cuprous-thiolate cluster

    PMID:9585572

    Open questions at the time
    • Did not assign individual coordinating cysteines
    • Physiological oxidation state and oligomeric form unresolved
  4. 2000 High

    Identified the Cys-Cys-Xaa-Cys motif as functionally essential and separated the requirement for copper binding from in vivo function, indicating function depends on more than metal coordination alone.

    Evidence Site-directed mutagenesis with respiratory growth, COX activity, Cu(I) binding, and import readouts in yeast

    PMID:10970896

    Open questions at the time
    • Why Cys mutants that still bind copper are non-functional was unexplained
    • Did not define the role of disulfides versus thiols
  5. 2001 High

    Linked oligomeric state to function, showing tetramerization correlates with mitochondrial localization and physiological activity.

    Evidence XAS, analytical ultracentrifugation, mutagenesis, and subcellular fractionation of yeast Cox17

    PMID:11170391

    Open questions at the time
    • Functional necessity of tetramer for copper transfer not directly tested
    • Relationship between oligomerization and redox state unclear
  6. 2003 High

    Resolved the long-standing question of where Cox17 acts by confining its function to the IMS and mapping a separable membrane-retention helix.

    Evidence Inner-membrane tethering fusion with respiratory complementation and domain mapping in yeast

    PMID:14615477

    Open questions at the time
    • Did not address the reported cytosolic pool's function
    • Mechanism of IMS retention by the amphipathic helix not detailed
  7. 2004 High

    Demonstrated Cox17 directly and specifically metallates both Sco1 and Cox11, defining the two downstream copper acceptors and revealing genetically separable transfer pathways.

    Evidence In vitro Cu(I) transfer with purified proteins, C57Y mutant dissection, and yeast cytoplasmic co-expression

    PMID:15199057

    Open questions at the time
    • Did not resolve why C57Y selectively loses the Sco1 route
    • Stoichiometry and complex intermediates of transfer not defined here
  8. 2004 Medium

    Placed Cox23 upstream of Cox17 in the same assembly pathway, hinting at a multi-step copper relay without a stable Cox17-Cox23 complex.

    Evidence Genetic epistasis by high-copy COX17 rescue, fractionation, and exclusion Co-IP in yeast

    PMID:15145942

    Open questions at the time
    • The biochemical activity of Cox23 and the nature of its handoff to Cox17 unknown
    • Transient interaction not excluded
  9. 2004 High

    Quantified the redox-state-dependent metal-binding hierarchy, showing oxidation tunes copper capacity from four ions to one to none.

    Evidence ESI-MS, fluorescence, and DTT competition on porcine Cox17

    PMID:15142040

    Open questions at the time
    • Physiologically active oxidation state in vivo not pinned down
    • Functional role of Zn(II) binding unclear
  10. 2004 High

    Provided the first apo-structure showing an intrinsically disordered N-terminus that becomes ordered on Cu(I) binding via a two-coordinate Atx1-like site.

    Evidence NMR solution structure and ITC of yeast apo-Cox17

    PMID:15465825

    Open questions at the time
    • Structure of the metallated transfer-competent state not solved here
    • Disulfide topology not yet integrated
  11. 2005 High

    Defined the disulfide-folded oxidized structure and a required disulfide isomerization step preceding copper binding, framing oxidation as the maturation switch.

    Evidence NMR structures of oxidized apoCox17 and biochemical analysis of redox/metal states

    PMID:15893662

    Open questions at the time
    • The catalyst of the required disulfide isomerization not identified here
    • Coupling of isomerization to import not yet shown
  12. 2006 High

    Connected Cox17-dependent Sco1 metallation to human disease by showing a patient SCO1 mutation blocks copper transfer without disrupting Sco1 metal binding.

    Evidence In vitro and yeast transfer assays, pulse-chase, and patient fibroblast analysis of SCO1 P174L

    PMID:16520371

    Open questions at the time
    • The structural basis of the transfer-specific defect not resolved
    • Whether COX17 mutations themselves cause disease not addressed
  13. 2007 High

    Established the human Cox17²ˢ⁻ˢ structure with the novel Cys-Cys copper coordination motif and linked Mia40-mediated oxidation to IMS trapping and copper-binding competence.

    Evidence NMR solution structure, redox potential measurement, and localization of human Cox17

    PMID:18093982

    Open questions at the time
    • Direct demonstration of Mia40 oxidation of Cox17 in vivo not shown here
    • Kinetics of import-coupled folding undefined
  14. 2007 High

    Measured redox midpoint potentials defining the energetics that govern interconversion among the three oxidation states and their distinct copper capacities.

    Evidence Electrochemical redox titration, XAS, and ESI-MS on mammalian Cox17

    PMID:17672825

    Open questions at the time
    • In vivo redox poise of the IMS Cox17 pool not determined
    • Coupling of potentials to physiological redox partners not tested
  15. 2008 High

    Revealed that copper transfer to Sco1 is mechanistically coupled to a two-electron transfer through a metal-bridged complex, explaining the Sco1/Sco2 transfer specificity.

    Evidence In vitro coupled copper/electron transfer with NMR detection of the intermediate complex and redox analysis

    PMID:18458339

    Open questions at the time
    • Structural model of the transient Cox17-Sco1 complex not resolved
    • Source of reducing equivalents (GSH) regulation in vivo unquantified
  16. 2009 Medium

    Demonstrated in human cells that loss of Cox17 specifically blocks copper delivery to Cox2, with loss of supercomplexes and accumulation of a Cox1-containing, Cox2-deficient intermediate.

    Evidence siRNA knockdown, BN-PAGE, and COX activity assay in HeLa cells

    PMID:19393246

    Open questions at the time
    • Direct linkage of the 150 kDa intermediate to copper status not biochemically proven
    • Effects on Cox1 Cu_B metallation not separately assessed
  17. 2011 High

    Dissected the distinct structural roles of the two disulfides, separating interhelical stabilization from copper-site organization.

    Evidence NMR structure and backbone dynamics of single-disulfide human Cox17 mutants

    PMID:21816817

    Open questions at the time
    • Functional copper-transfer competence of single-disulfide forms not tested
    • In vivo abundance of these intermediate forms unknown
  18. 2015 Medium

    Extended Cox17 function beyond copper relay by showing a copper-regulated interaction with Mic60 that modulates MICOS integrity and inner-membrane architecture.

    Evidence Co-IP, genetic interaction, and MICOS integrity assays

    PMID:25918166

    Open questions at the time
    • Single-lab Co-IP without structural mapping of the interface
    • Whether this is a moonlighting role or coupled to copper delivery unclear
  19. 2015 Medium

    Identified Cox17 as a facilitator of cisplatin delivery to mitochondria, with glutathione gating platinum loading.

    Evidence Kinetic binding, platinum transfer, and aggregation assays in vitro

    PMID:26399480

    Open questions at the time
    • In vivo relevance to cisplatin pharmacology not established
    • Single in vitro study
  20. 2016 Medium

    Localized cisplatin binding to the Cu(I)-coordinating cysteines, defining competitive metal/drug coordination at the chaperone's active site.

    Evidence Top-down FT-ICR MS/MS with electron capture dissociation

    PMID:27539433

    Open questions at the time
    • Single-method site assignment without orthogonal confirmation
    • Functional consequence for copper chaperone activity not measured
  21. 2019 Medium

    Confirmed the human copper-chaperone role with a clean phenotype linking COX17 loss to reduced mitochondrial copper, COX subassembly accumulation, and cristae defects.

    Evidence Stable shRNA knockdown, copper quantification, BN-PAGE, EM, and western blot in HEK293 cells

    PMID:31903891

    Open questions at the time
    • Single-lab study
    • Did not distinguish direct copper-delivery defect from secondary mitochondrial damage
  22. 2023 High

    Identified MOF-KANSL acetylation as a positive regulatory input controlling Cox17 activity and complex IV integrity.

    Evidence MOF KO/KD, acetylation-mimetic and non-acetylatable mutants, complex IV assays, EM, and patient fibroblast rescue

    PMID:37813994

    Open questions at the time
    • Acetylated residue's effect on copper binding/transfer mechanism not resolved
    • Deacetylase and physiological signals tuning acetylation unknown
  23. 2023 Medium

    Revealed inducible mitochondrial import of COX17 via the AIF/CHCHD4 pathway as a route by which lead exposure drives mitochondrial copper overload and damage.

    Evidence APP/PS1 mouse and BV-2 cell models, copper quantification, fractionation, and pathway inhibition

    PMID:38091880

    Open questions at the time
    • Whether enhanced import reflects increased flux through normal machinery or a stress-specific route unclear
    • Single-lab study
  24. 2023 Medium

    Showed COX17 acts bidirectionally in mitochondrial copper homeostasis, both maintaining complex IV and discharging excess copper.

    Evidence UUO and TGF-β1 fibrosis models with COX17 knockdown and overexpression, activity assays, and copper quantification

    PMID:37217601

    Open questions at the time
    • Molecular basis of copper efflux/discharge function not defined
    • Single-lab study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple Cox17 functions—copper relay, MICOS modulation, acetylation control, and copper efflux—are integrated and prioritized in vivo, and whether COX17 variants directly cause human complex IV disease, remain open.
  • No structural model of the transfer-competent Cox17-Sco1/Cox11 complexes in cells
  • No reported COX17 disease mutation despite established pathway relevance
  • Mechanism of copper discharge/efflux unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140104 molecular carrier activity 3 GO:0140313 molecular sequestering activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005739 mitochondrion 2 GO:0005829 cytosol 2
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-1852241 Organelle biogenesis and maintenance 3
Partners
COX11MIC60MOFSCO1

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 COX17 encodes a cytoplasmic cysteine-rich protein required for a late post-translational step in cytochrome c oxidase assembly; a cox17 null mutant is rescued by copper supplementation, establishing a specific role in delivering copper to mitochondria rather than general copper metabolism. Genetic complementation, null mutant rescue with copper supplementation, subunit expression analysis The Journal of biological chemistry High 8662933
1998 Yeast Cox17 binds copper as a binuclear cuprous-thiolate cluster with trigonally coordinated Cu(I) ions (three Cu-S bonds at 2.26 Å, Cu-Cu distance of 2.7 Å); the cluster is more labile than metallothionein clusters, consistent with a copper-delivery chaperone function. X-ray absorption spectroscopy (EXAFS), UV-visible absorption and emission spectroscopy Biochemistry High 9585572
2000 Mutational analysis of yeast Cox17 identified three cysteines in a Cys-Cys-Xaa-Cys motif (residues 23, 24, 26) as critical for function; single Cys→Ser substitutions abolish cytochrome oxidase activity and respiratory growth without preventing Cu(I) binding or mitochondrial import, whereas the C57Y mutant fails to accumulate in mitochondria. Site-directed mutagenesis, respiratory growth assays, cytochrome oxidase activity measurement, Cu(I) binding assays The Journal of biological chemistry High 10970896
2001 Cox17 purified without a tag binds three Cu(I) ions per monomer in a polycopper cluster and exists in a dimer/tetramer equilibrium (Kd ~20 µM); Cys23, Cys24, or Cys26 substitutions abolish tetramerization and function without preventing Cu(I) binding, implicating oligomeric state in physiological function. Mitochondrial Cox17 is predominantly tetrameric; cytosolic Cox17 is primarily dimeric. X-ray absorption spectroscopy, analytical ultracentrifugation, site-directed mutagenesis, subcellular fractionation Biochemistry High 11170391
2003 Cox17 tethered to the mitochondrial inner membrane via a Sco2 transmembrane fusion fully rescues cox17Δ cells for respiratory growth and cytochrome oxidase activity, demonstrating that Cox17 function is confined to the mitochondrial intermembrane space. A C-terminal amphipathic helix is required for mitochondrial retention and is spatially separable from the N-terminal copper-binding domain. Mitochondrial membrane tethering fusion protein, respiratory growth complementation, cytochrome oxidase activity assay, domain mapping The Journal of biological chemistry High 14615477
2004 Cox17 directly transfers Cu(I) to both Sco1 and Cox11 in vitro with high specificity (no transfer to BSA or carbonic anhydrase); a C57Y Cox17 mutant can transfer copper to Cox11 but not to Sco1, distinguishing the two transfer pathways. Transfer was corroborated by a yeast cytoplasmic co-expression system. In vitro copper transfer assay with purified proteins, yeast cytoplasm co-expression system, site-directed mutagenesis The Journal of biological chemistry High 15199057
2004 NMR solution structure of yeast apo-Cox17 reveals two α-helices preceded by an intrinsically disordered N-terminal region; Cu(I) is coordinated by Cys23 and Cys26 in a two-coordinate site similar to Atx1-family chaperones, and Cu(I) binding orders the copper-binding region. ITC shows fully reduced Cox17 binds one Cu(I) with Ka ~6×10⁶ M⁻¹. NMR solution structure determination, isothermal titration calorimetry (ITC) The Journal of biological chemistry High 15465825
2004 Cox23p, a Cox17 homolog, is required for cytochrome oxidase assembly and operates upstream of Cox17 in the same pathway; Cox23p and Cox17p are not part of a stable complex with each other, and both localize to the mitochondrial intermembrane space and cytosol. Genetic epistasis (null mutant rescue by copper supplementation requires high-copy COX17), subcellular fractionation, co-immunoprecipitation (excluded complex) The Journal of biological chemistry Medium 15145942
2004 Porcine Cox17 binds cooperatively four Cu⁺ ions forming a Cu₄S₆-type cluster; it also binds non-cooperatively two Zn²⁺ ions but not Ag⁺, demonstrating high metal-binding specificity. Partially oxidized Cox17 (two disulfide bonds) binds one Cu⁺ or Zn²⁺; fully oxidized Cox17 (three disulfide bonds) binds no metals. Electrospray ionization mass spectrometry (ESI-MS), fluorescence spectroscopy, DTT competition assay The Biochemical journal High 15142040
2005 NMR solution structure of oxidized apoCox17 reveals a coiled-coil fold stabilized by two disulfide bonds (Cys26/Cys57 and Cys36/Cys47); isomerization of the Cys26/Cys57 disulfide to Cys24/Cys57 is required prior to Cu(I) binding. A third fully oxidized form cannot bind copper; fully reduced Cox17 forms a molten globule that can bind up to four Cu(I) ions in a polycopper cluster and is oligomeric. NMR solution structure, disulfide bond analysis, Cu(I) binding assays Structure High 15893662
2006 The P174L mutation in human Sco1 severely compromises Cox17-dependent copper transfer to Sco1 in vitro and in a yeast cytoplasmic assay, but retains normal Cu(I) and Cu(II) binding; failure of Cox17-mediated metallation of Sco1 leads to rapid turnover of CoxII and COX assembly defects in patient fibroblasts. In vitro copper transfer assay, yeast cytoplasmic assay, pulse-chase labeling, patient fibroblast analysis The Journal of biological chemistry High 16520371
2007 NMR solution structure of human Cox17 (Cox17²ˢ⁻ˢ) reveals a coiled-coil-helix-coiled-coil-helix domain stabilized by disulfides Cys25-Cys54 and Cys35-Cys44, with an unstructured N-terminal tail; Cu(I) is coordinated by Cys22 and Cys23 (Cys-Cys motif, first example in copper proteins). Redox measurements support that unstructured fully reduced Cox17 enters the IMS where Mia40-mediated oxidation to Cox17²ˢ⁻ˢ traps it and enables copper binding. NMR solution structure, redox potential measurements, subcellular localization analysis The Journal of biological chemistry High 18093982
2007 Mammalian Cox17 exists in three oxidative states with distinct metal-binding properties: Cox17⁰ˢ⁻ˢ (fully reduced) binds four Cu⁺ cooperatively; Cox17²ˢ⁻ˢ (two disulfides) binds one Cu⁺ or Zn²⁺; Cox17³ˢ⁻ˢ (three disulfides) binds no metals. Redox midpoint potentials: Em1 = -197 mV (Cox17³ˢ⁻ˢ↔Cox17²ˢ⁻ˢ), Em2 = -340 mV (Cox17²ˢ⁻ˢ↔Cox17⁰ˢ⁻ˢ). XAS confirms a Cu₄S₆-type cluster in Cu₄Cox17. Redox potential determination, X-ray absorption spectroscopy (XAS), ESI-MS The Biochemical journal High 17672825
2008 Human Cox17²ˢ⁻ˢ loaded with Cu(I) transfers copper and two electrons simultaneously to oxidized HSco1 (disulfide form), yielding Cu(I)HSco1 and fully oxidized apoHCox17³ˢ⁻ˢ; glutathione can reduce apoHCox17³ˢ⁻ˢ back to Cox17²ˢ⁻ˢ. This coupled copper-electron transfer does not occur with HSco2 due to lack of a specific metal-bridged protein-protein complex. In vitro copper transfer assay with purified proteins, NMR spectroscopy to detect protein-protein complex, redox analysis Proceedings of the National Academy of Sciences of the United States of America High 18458339
2009 COX17 siRNA knockdown in HeLa cells reduces cytochrome c oxidase activity and assembly; COX-containing respiratory supercomplexes disappear as an early response, and a novel ~150 kDa complex accumulates containing Cox1 but not Cox2, suggesting Cox17 absence specifically impairs copper delivery to Cox2. siRNA knockdown, blue native gel electrophoresis, cytochrome c oxidase activity assay Journal of molecular biology Medium 19393246
2011 Structural analysis of human Cox17 mutants with single disulfide bonds shows the inner disulfide (Cys36-Cys45) stabilizes interhelical hydrophobic interactions and is sufficient to maintain the mature Cox17 structure/dynamics, while the external disulfide (Cys26-Cys55) organizes the copper-binding site region but cannot stabilize interhelical packing. NMR structure determination and backbone mobility analysis of Cox17 disulfide mutants The Journal of biological chemistry High 21816817
2015 Cox17 directly interacts with Mic60 of the MICOS complex, modulating MICOS integrity and inner mitochondrial membrane architecture; this interaction is independent of Sco1 but is regulated by copper ions. Co-immunoprecipitation, genetic interaction analysis, MICOS complex integrity assays The Journal of biological chemistry Medium 25918166
2015 Cox17 facilitates delivery of cisplatin to mitochondria; glutathione significantly modulates platinum binding to Cox17, with cisplatin-GSH adducts transferring >90% platinum to Cox17, while transplatin-GSH adducts are inert to Cox17, and GSH attenuates Cox17 aggregation induced by platination. Kinetic binding assays, platinum transfer assays, protein aggregation assays The Biochemical journal Medium 26399480
2016 Cisplatin binds to human Cox17²ˢ⁻ˢ primarily at Cys26 or Cys27 (the Cu(I)-binding site), as determined by top-down FT-ICR-MS/MS with electron capture dissociation, demonstrating competitive coordination with cuprous ions. High-resolution FT-ICR tandem mass spectrometry with electron capture dissociation (ECD) Rapid communications in mass spectrometry Medium 27539433
2019 Stable COX17 shRNA knockdown in HEK293 cells causes decreased intramitochondrial copper content, reduced levels of COX subunits (Cox1, Cox4, Cox5a), accumulation of COX subcomplexes, and mitochondrial ultrastructural changes including cristae reduction and mitochondrial swelling, confirming copper chaperone role in human cells. Stable shRNA knockdown, copper quantification, BN-PAGE, electron microscopy, western blot Folia biologica Medium 31903891
2023 COX17 is acetylated by the MOF-KANSL lysine acetyltransferase complex; loss of MOF or COX17, or expression of non-acetylatable COX17 mutant, causes mitochondrial fragmentation, reduced cristae density, and impaired complex IV integrity; acetylation-mimetic COX17 rescues complex IV activity even in absence of MOF, establishing activatory role of COX17 acetylation. MOF knockout/knockdown, site-directed mutagenesis (acetylation-mimetic and non-acetylatable mutants), mitochondrial complex IV activity assay, electron microscopy, patient fibroblast complementation Nature metabolism High 37813994
2023 Lead (Pb) exposure enhances mitochondrial translocation of COX17 via the AIF/CHCHD4 mitochondrial import pathway, increasing mitochondrial copper concentration and causing mitochondrial damage in microglia; copper-chelating agents or inhibition of COX17 mitochondrial translocation reverses this effect. In vivo APP/PS1 mouse model, in vitro BV-2 cell model, copper quantification, mitochondrial fractionation, pathway inhibition Redox biology Medium 38091880
2023 COX17 knockdown in fibrotic kidney models aggravates mitochondrial copper accumulation and inhibits complex IV activity, while COX17 overexpression discharges excess mitochondrial copper and restores complex IV function, demonstrating a bidirectional role of COX17 in mitochondrial copper homeostasis and complex IV maintenance. UUO mouse model, TGF-β1 in vitro fibrosis model, COX17 knockdown and overexpression, complex activity assays, copper quantification Acta pharmacologica Sinica Medium 37217601
1997 A human cDNA encoding a protein homologous to yeast Cox17p functionally complements a yeast cox17 null mutant for respiratory growth, establishing functional conservation of the copper-delivery mechanism in human cells. Functional complementation of yeast cox17 null mutant with human cDNA expression library Human genetics High 9050918

Source papers

Stage 0 corpus · 39 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Characterization of COX17, a yeast gene involved in copper metabolism and assembly of cytochrome oxidase. The Journal of biological chemistry 396 8662933
2004 Specific copper transfer from the Cox17 metallochaperone to both Sco1 and Cox11 in the assembly of yeast cytochrome C oxidase. The Journal of biological chemistry 244 15199057
2008 Mitochondrial copper(I) transfer from Cox17 to Sco1 is coupled to electron transfer. Proceedings of the National Academy of Sciences of the United States of America 162 18458339
1997 Isolation of a cDNA encoding the human homolog of COX17, a yeast gene essential for mitochondrial copper recruitment. Human genetics 126 9050918
2001 The mitochondrial copper metallochaperone Cox17 exists as an oligomeric, polycopper complex. Biochemistry 113 11170391
2005 Folding studies of Cox17 reveal an important interplay of cysteine oxidation and copper binding. Structure (London, England : 1993) 108 15893662
2003 Cox17 is functional when tethered to the mitochondrial inner membrane. The Journal of biological chemistry 97 14615477
1998 Characterization of the copper chaperone Cox17 of Saccharomyces cerevisiae. Biochemistry 93 9585572
2004 Yeast cox17 solution structure and Copper(I) binding. The Journal of biological chemistry 91 15465825
2007 A structural-dynamical characterization of human Cox17. The Journal of biological chemistry 86 18093982
2000 Mutational analysis of the mitochondrial copper metallochaperone Cox17. The Journal of biological chemistry 85 10970896
2004 Metal-binding mechanism of Cox17, a copper chaperone for cytochrome c oxidase. The Biochemical journal 81 15142040
2004 COX23, a homologue of COX17, is required for cytochrome oxidase assembly. The Journal of biological chemistry 70 15145942
2003 Identification of COX17 as a therapeutic target for non-small cell lung cancer. Cancer research 67 14612491
2023 Lead aggravates Alzheimer's disease pathology via mitochondrial copper accumulation regulated by COX17. Redox biology 61 38091880
2007 Oxidative switches in functioning of mammalian copper chaperone Cox17. The Biochemical journal 51 17672825
2009 Knockdown of human COX17 affects assembly and supramolecular organization of cytochrome c oxidase. Journal of molecular biology 49 19393246
2023 COX17 restricts renal fibrosis development by maintaining mitochondrial copper homeostasis and restoring complex IV activity. Acta pharmacologica Sinica 45 37217601
2015 Cox17 Protein Is an Auxiliary Factor Involved in the Control of the Mitochondrial Contact Site and Cristae Organizing System. The Journal of biological chemistry 41 25918166
2000 Characterization and localization of human COX17, a gene involved in mitochondrial copper transport. Human genetics 32 10982038
2000 Characterization of human SCO1 and COX17 genes in mitochondrial cytochrome-c-oxidase deficiency. Biochemical and biophysical research communications 30 11027508
2006 The P174L mutation in human Sco1 severely compromises Cox17-dependent metallation but does not impair copper binding. The Journal of biological chemistry 29 16520371
2023 COX17 acetylation via MOF-KANSL complex promotes mitochondrial integrity and function. Nature metabolism 27 37813994
2019 Stable COX17 Downregulation Leads to Alterations in Mitochondrial Ultrastructure, Decreased Copper Content and Impaired Cytochrome c Oxidase Biogenesis in HEK293 Cells. Folia biologica 22 31903891
2002 Characterization and identification of promoter elements in the mouse COX17 gene. Biochimica et biophysica acta 21 11997103
2015 Glutathione selectively modulates the binding of platinum drugs to human copper chaperone Cox17. The Biochemical journal 16 26399480
2011 Functional role of two interhelical disulfide bonds in human Cox17 protein from a structural perspective. The Journal of biological chemistry 16 21816817
2022 Zebrafish cox17 modulates primitive erythropoiesis via regulation of mitochondrial metabolism to facilitate hypoxia tolerance. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 15 36208295
2006 Cox17, a copper chaperone for cytochrome c oxidase: expression, purification, and formation of mixed disulphide adducts with thiol reagents. Protein expression and purification 14 17208454
2019 Transcriptional profiles and copper stress responses in zebrafish cox17 mutants. Environmental pollution (Barking, Essex : 1987) 11 31662245
2018 The nonsense-mediated mRNA decay (NMD) pathway differentially regulates COX17, COX19 and COX23 mRNAs. Current genetics 11 30317392
2014 Identification and initial characterisation of a Plasmodium falciparum Cox17 copper metallochaperone. Experimental parasitology 11 25447123
2016 Identification of binding sites of cisplatin to human copper chaperone protein Cox17 by high-resolution FT-ICR-MS. Rapid communications in mass spectrometry : RCM 7 27539433
2009 Modulation of redox switches of copper chaperone Cox17 by Zn(II) ions determined by new ESI MS-based approach. Antioxidants & redox signaling 6 19018666
2001 Genomic structure of mouse copper chaperone, COX17. DNA sequence : the journal of DNA sequencing and mapping 4 11913776
2016 A comparative study on the interactions of human copper chaperone Cox17 with anticancer organoruthenium(II) complexes and cisplatin by mass spectrometry. Journal of inorganic biochemistry 2 27235272
2025 Cisplatin transported by COX17 induces cochlear damage by binding Myosin IIA to regulate cell pyroptosis induced by mitochondrial dysfunction. Life sciences 1 40945651
2026 COX17 Attenuates Diabetes-Associated Retinal Injury by Improving Mitochondrial Function. Clinical and experimental pharmacology & physiology 0 41347662
2026 Lysophosphatidylcholine acyltransferase 1 promotes head and neck squamous cell carcinoma progression by enhancing COX17-dependent oxidative phosphorylation. Cell death discovery 0 41792107

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