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Showing COX4I1 — COX4 is a alias.

COX4I1

Cytochrome c oxidase subunit 4 isoform 1, mitochondrial · UniProt P13073

Length
169 aa
Mass
19.6 kDa
Annotated
2026-06-09
33 papers in source corpus 16 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COX4I1 encodes the regulatory subunit 4 isoform 1 of cytochrome c oxidase (mitochondrial Complex IV), a structural and assembly-critical component of the oxidative phosphorylation machinery (PMID:28766551, PMID:33578848). The subunit coordinates a buried Zn(II) ion through one histidine and three cysteine residues, and disruption of the cysteine ligands abolishes cytochrome oxidase assembly, establishing zinc binding as essential for complex stability (PMID:17215247). Loss of COX4I1 not only abolishes Complex IV assembly but also produces a profound secondary deficiency of Complex I, with accumulation of Complex I assembly intermediates and reduced mitochondrial translation of both cIV and cI subunits, and prevents formation of cI/cIII/cIV supercomplexes (PMID:33578848); conversely, COX4-1 promotes supercomplex assembly and lowers superoxide production (PMID:35478774). Pathogenic COX4I1 variants reduce subunit protein levels and impair Complex IV assembly and activity, causing decreased COX activity, impaired ATP production, and elevated ROS, defining COX4I1 as the basis of a mitochondrial disease (PMID:28766551, PMID:41203052). Beyond its core bioenergetic role, COX4I1 expression is controlled post-transcriptionally by miR-338 (PMID:33933660) and transcriptionally downstream of HIF-1α (PMID:29991768), and the isoform context (COX4-1 versus COX4-2) tunes redox metabolism to divert cell death from ferroptosis toward apoptosis (PMID:41596099) and modulates chemo- and radioresistance in tumor cells (PMID:28455961, PMID:35478774). A persistent COX4I1–Dynll1 complex whose dissociation gates mitochondrial ROS release links the subunit to innate antibacterial responses (PMID:32041786). Translational control of the yeast ortholog by membrane phospholipid content and polyamines via 5' UTR stem-loop elements has been characterized (PMID:16428432, PMID:19695341), and a direct arachidonoyl-PE interaction at the COX4I1 interface enhancing electron transport efficiency has been described [PMID:bio_10.1101_2025.05.15.654206].

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2006 High

    Established that synthesis of the Cox4 subunit is coupled to mitochondrial membrane lipid status, answering how the cell coordinates subunit production with membrane integrity.

    Evidence Reporter fusions, 5' UTR deletion mapping, and RNA-protein binding in cardiolipin/phosphatidylglycerol-deficient yeast

    PMID:16428432

    Open questions at the time
    • The trans-acting repressor protein was not molecularly identified
    • Whether the human 5' UTR is regulated equivalently was not tested
  2. 2007 High

    Defined the structural basis of the subunit's contribution to complex stability, showing zinc coordination is required for cytochrome oxidase assembly.

    Evidence NMR solution structure plus site-directed mutagenesis of Zn-coordinating Cys residues and functional assembly assays in yeast Cox4

    PMID:17215247

    Open questions at the time
    • Structure is of the yeast ortholog, not human COX4I1
    • Functional role of the buried zinc beyond folding/stability not resolved
  3. 2009 Medium

    Extended translational regulation of the subunit to polyamine control, identifying COX4 as a member of a polyamine modulon acting through 5' UTR ribosome shunting.

    Evidence Polyamine-requiring yeast mutant with spermidine add-back and translation-level analysis

    PMID:19695341

    Open questions at the time
    • Single lab; orthogonal validation limited
    • Mechanism of ribosome shunting on the stem-loops not dissected
    • Human relevance untested
  4. 2017 High

    Demonstrated COX4I1 is essential for human Complex IV function and disease-causing, by showing a patient mutation ablates protein and enzyme activity and that wild-type cDNA rescues.

    Evidence Whole exome sequencing, patient fibroblast enzymatic assays, and lentiviral complementation

    PMID:28766551

    Open questions at the time
    • Single patient/family
    • Mechanism by which the K101N variant destabilizes the protein not detailed
  5. 2017 Medium

    Showed that COX4 isoform identity confers differential pharmacological sensitivity of Complex IV, linking the COX4-2-to-COX4-1 switch to chemoresistance.

    Evidence COX activity assays in COX4-1 vs COX4-2 glioma cells, computational docking, and orthotopic tumor models

    PMID:28455961

    Open questions at the time
    • Chlorpromazine binding site is computationally inferred, not structurally resolved
    • Causal driver of the isoform switch not established
  6. 2018 Medium

    Placed COX4I1 downstream of HIF-1α in a mitochondrial stress-response circuit, addressing how the subunit is transcriptionally tuned to oxidative stress.

    Evidence HIF-1α inhibition with COX activity, ROS, ATP, and membrane potential readouts in neuron-like cells

    PMID:29991768

    Open questions at the time
    • Direct HIF-1α binding to the COX4I1 promoter not shown
    • Restricted to a single in vitro model
  7. 2020 Medium

    Identified a Dynll1-COX4I1 complex as a gate for mitochondrial ROS release, connecting the subunit to innate immune control of bacterial proliferation.

    Evidence Mass spectrometry, Co-IP, and a Listeria infection model in dendritic cells with ROS measurement

    PMID:32041786

    Open questions at the time
    • Single Co-IP-based interaction without reciprocal structural validation
    • Mechanism by which dissociation triggers ROS release unresolved
  8. 2021 High

    Revealed that COX4I1 loss impairs not only Complex IV but Complex I biogenesis and supercomplex formation, partly via attenuated mitochondrial translation, broadening its role beyond a single complex.

    Evidence CRISPR KO with blue-native PAGE, pulse-chase metabolic labeling, and complexome profiling in HEK293

    PMID:33578848

    Open questions at the time
    • The molecular link between cIV deficiency and reduced mitochondrial translation is not defined
    • Generalizability across cell types untested
  9. 2021 Medium

    Identified miR-338 as a direct post-transcriptional regulator of COX4I1 controlling CcO activity and ATP, establishing COX4I1 as the effector of miR-338 in ischemic stress.

    Evidence miR-338 antagomir plus COX4I1 siRNA epistasis with CcO activity and ATP readouts in astrocytes/neurons

    PMID:33933660

    Open questions at the time
    • Direct miR-338 binding to the COX4I1 transcript not biochemically mapped
    • Single lab
  10. 2022 High

    Showed COX4-1 drives supercomplex assembly and suppresses superoxide, linking the subunit to radioresistance through redox control.

    Evidence Reciprocal overexpression/silencing in isogenic GBM lines with CcO activity, superoxide, and native PAGE supercomplex analysis

    PMID:35478774

    Open questions at the time
    • Structural basis for supercomplex-promoting activity unresolved
    • Whether superoxide reduction is cause or consequence of SC assembly not separated
  11. 2022 Medium

    Connected COX4-1 deficiency to nuclear genome maintenance, showing mitochondrial dysfunction drives DNA damage accumulation and premature senescence.

    Evidence COX4I1 siRNA knockdown with DNA damage markers and genotoxic recovery assays in fibroblasts

    PMID:35456968

    Open questions at the time
    • The mitochondria-to-nucleus signaling link is correlative
    • Mechanism connecting OXPHOS loss to reduced DNA repair expression undefined
  12. 2024 High

    Defined COX4I1 as a survival dependency in AML whose loss triggers ferroptosis, identifying functional regions and a therapeutic synergy with venetoclax.

    Evidence CRISPR screen and gene tiling, mitochondrial proteomics, ferroptosis assays, and in vivo AML models

    PMID:39716856

    Open questions at the time
    • The specific molecular function of the essential tiled regions not resolved
    • Mechanistic basis of ferroptosis induction by depletion not fully defined
  13. 2024 Medium

    Showed COX4I1 regulates trophoblast invasion through MMP1, linking the subunit's metabolic role to a downstream effector of cell behavior.

    Evidence siRNA knockdown with proliferation/invasion assays, Seahorse metabolic analysis, and MMP1 rescue in EVT cells

    PMID:38718733

    Open questions at the time
    • How metabolic change is transduced to MMP1 regulation is unknown
    • Single lab in primary cells
  14. 2025 High

    Used transmitochondrial cybrids to isolate the mitochondrial COX4-1 contribution, showing isoform identity rewires redox metabolism and switches cell death mode from ferroptosis to apoptosis.

    Evidence POLG-KO ρ0 cells reconstituted with COX4-1 vs COX4-2 mitochondria, erastin treatment, iron/cystine uptake, and SLC7A11/GPX4 analysis

    PMID:41596099

    Open questions at the time
    • Molecular pathway from CcO activity to SLC7A11/GPX4 regulation undefined
    • Single lab
  15. 2025 Medium

    Generalized the disease mechanism, showing diverse pathogenic variants converge on reduced COX4I1 protein impairing Complex IV assembly with downstream mitoribosomal effects.

    Evidence Patient fibroblast functional studies, transfected cell lines, Complex IV assays, and proteomics

    PMID:41203052

    Open questions at the time
    • Limited number of cases
    • Causal link between subunit loss and mitoribosomal changes not mechanistically dissected

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular mechanism coupling COX4I1/Complex IV status to nuclear DNA repair, mitochondrial translation, and the ferroptosis-versus-apoptosis decision remains undefined.
  • No defined signaling pathway from CcO activity to nuclear DNA damage response
  • Mechanism linking cIV loss to attenuated mitochondrial protein synthesis unknown
  • No human structural model of COX4I1 within assembled Complex IV reported in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 3 GO:0005198 structural molecule activity 2
Localization
GO:0005739 mitochondrion 4
Pathway
R-HSA-1430728 Metabolism 2 R-HSA-5357801 Programmed Cell Death 2
Partners
DYNLL1
Complex memberships
cytochrome c oxidase (Complex IV)mitochondrial respiratory supercomplex (cI/cIII/cIV)

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 Yeast Cox4 (ortholog of human COX4I1) is a zinc-binding subunit of cytochrome c oxidase. The Zn(II) coordination involves a single histidyl residue and three conserved cysteine residues. Substitutions at the Cys ligand positions result in non-functional Cox4 proteins that fail to support cytochrome oxidase assembly, demonstrating that zinc binding is essential for complex stability. NMR solution structure revealed a C-terminal globular domain with two beta sheets, with the Zn(II) ion buried within the domain. NMR structure determination, site-directed mutagenesis of zinc-coordinating residues, functional assembly assays The Journal of biological chemistry High 17215247
2006 Translation of yeast COX4 mRNA is regulated by phosphatidylglycerol and cardiolipin content in mitochondrial membranes. A 50-nucleotide cis-element with two stem-loops in the 5' UTR of COX4 mRNA inhibits translation when cardiolipin/phosphatidylglycerol are absent, and a trans-acting protein factor(s) from the cytoplasm of cardiolipin-deficient cells specifically binds this cis-element to repress translation. Reporter gene (mtGFP) fusions, 5' UTR deletion analysis, RNA-protein binding assay, genetic complementation Molecular and cellular biology High 16428432
2009 Spermidine stimulates translation of yeast COX4 mRNA approximately 2.5-fold by promoting ribosome shunting through stem-loop structures in the 5' UTR, making COX4 the first member of a polyamine modulon in yeast. Polyamine-requiring yeast mutant (Δspe1), spermidine add-back experiments, translation-level analysis The international journal of biochemistry & cell biology Medium 19695341
2017 COX4I1 (COX4-1) is a regulatory subunit of cytochrome c oxidase (Complex IV). A K101N mutation in COX4I1 leads to decreased COX activity, impaired ATP production, elevated ROS, and undetectable COX4-1 protein in patient fibroblasts. Lentiviral transduction with wild-type COX4I1 restored COX activity and ATP production, confirming the essential role of COX4-1 in Complex IV function. Whole exome sequencing, Sanger confirmation, patient fibroblast enzymatic assays, lentiviral complementation European journal of human genetics : EJHG High 28766551
2017 Chlorpromazine selectively inhibits cytochrome c oxidase (Complex IV) activity in chemoresistant glioma cells expressing COX4-1, but not in chemosensitive cells expressing COX4-2, without affecting other mitochondrial complexes. Computer-simulated docking indicated chlorpromazine binds more tightly to CcO containing COX4-1 than COX4-2. The switch from COX4-2 to COX4-1 expression accompanies the development of chemoresistance. COX activity assays in chemoresistant vs. chemosensitive glioma cells, computer-simulated docking, orthotopic mouse brain tumor models Oncotarget Medium 28455961
2021 Complete knockout of COX4I1 in HEK293 cells abolishes Complex IV (cIV) assembly and also causes profound deficiency of Complex I (cI), with decreased cI subunit levels and reduced assembled cI. Supercomplexes (cI/cIII/cIV) were absent. Pulse-chase metabolic labeling revealed decreased mitochondrial translation of cIV and cI subunits, and complexome profiling revealed accumulation of cI assembly intermediates, indicating that cIV deficiency impairs cI biogenesis (rather than stability) partly through attenuation of mitochondrial protein synthesis. CRISPR KO, blue-native PAGE, pulse-chase metabolic labeling of mtDNA-encoded proteins, complexome profiling, quantitative proteomics Cells High 33578848
2022 COX4-1 expression promotes assembly of CcO-containing mitochondrial supercomplexes (SCs) in GBM cells and reduces superoxide production. Overexpression of COX4-1 in radiosensitive cells increased CcO activity, promoted SC assembly, and conferred radioresistance, while silencing COX4-1 in radioresistant cells reduced CcO activity, promoted SC disassembly, and increased superoxide production. Isogenic radiosensitive/radioresistant GBM cell lines, COX4-1 overexpression and siRNA silencing, CcO activity assays, superoxide measurements, native PAGE for SC analysis Cell stress High 35478774
2020 Dynein light chain 1 (Dynll1) forms a persistent protein complex with mitochondrial cytochrome oxidase Cox4i1. Dissociation of the Dynll1-Cox4i1 complex upon Listeria monocytogenes infection is required for the release of mitochondrial reactive oxygen species, which regulates intracellular bacterial proliferation. Dynll1 acts as an inhibitor of mitochondrial ROS production through this interaction. Mass spectrometry of membrane proteins, Co-IP/complex identification, bacterial infection model in dendritic cells, ROS measurement Infection and immunity Medium 32041786
2021 COX4I1 is a direct target of microRNA-338 (miR-338). Inhibition of miR-338 increased COX4I1 levels and augmented cytochrome c oxidase (CcO) activity and ATP production in astrocytes and neurons. The protective effect of miR-338 inhibitor against in vitro ischemia was blocked by concurrent COX4I1 siRNA knockdown, establishing COX4I1 as the relevant effector of miR-338 in mitochondrial ATP production. miR-338 antagomir treatment in vivo and in vitro, siRNA knockdown of COX4I1, CcO activity assays, ATP measurement, infarct size measurement Mitochondrion Medium 33933660
2018 HIF-1α regulates expression of COX4I1 (COXIV-1). In neuron-like cells, microwave-induced ROS production activated HIF-1α, which in turn upregulated COXIV-1 expression. HIF-1α inhibition downregulated COXIV-1, promoted ROS generation, impaired mitochondrial membrane potential, and abolished microwave-induced ATP production, indicating COX4I1 is downstream of HIF-1α in a mitochondrial stress-response pathway. HIF-1α inhibitor treatment, HIF-1α transcriptional activity assay, COX activity assays, ROS measurement, ATP measurement, mitochondrial membrane potential assay Scientific reports Medium 29991768
2024 COX4I1 depletion in AML cells induces mitochondrial stress and ferroptosis, disrupts mitochondrial ultrastructure and oxidative phosphorylation. CRISPR gene tiling scans combined with mitochondrial proteomics identified specific regions within COX4I1 essential for leukemia cell survival and mitochondrial Complex IV assembly. COX4I1 depletion or pharmacological inhibition of Complex IV (chlorpromazine) synergized with venetoclax. CRISPR screen, CRISPR gene tiling, mitochondrial proteomics, COX4I1 depletion, ferroptosis/apoptosis assays, venetoclax combination studies, in vivo AML progression assay Advanced science (Weinheim, Baden-Wurttemberg, Germany) High 39716856
2024 COX4I1 knockdown in extravillous trophoblast (EVT) cells inhibited proliferation, increased migration and invasion, impaired mitochondrial respiration and glycolysis, and induced mitochondrial fusion. Knockdown of MMP1 rescued the increased migration and invasion induced by COX4I1 silencing, placing MMP1 downstream of COX4I1 in the regulation of trophoblast invasion. siRNA knockdown, RTCA, EdU proliferation assay, Seahorse metabolic analysis, MitoTracker staining, MMP1 rescue experiment Placenta Medium 38718733
2022 COX4-1 deficiency (COX4I1 knockdown) in human fibroblasts leads to accumulative DNA damage primarily in proliferating cells, reduced DNA damage response pathway expression, impaired recovery from genotoxic insult, and decreased DNA repair, resulting in replicative stress and premature senescence. COX4I1 knockdown (siRNA), DNA damage marker analysis, genotoxic insult recovery assay, expression analysis of DNA repair pathways International journal of molecular sciences Medium 35456968
2025 In transmitochondrial cybrid cells, COX4-1-containing mitochondria restored CcO activity and conferred resistance to erastin-induced ferroptosis, whereas COX4-2 mitochondria did not. COX4-1 cybrids exhibited reduced labile iron, diminished cystine uptake, and low SLC7A11 and GPX4 expression, yet underwent apoptosis rather than ferroptosis upon erastin treatment, demonstrating that mitochondrial COX4-1 rewires redox metabolism and diverts cell death from ferroptosis to apoptosis. CRISPR POLG-KO ρ0 cells, transmitochondrial cybrid reconstitution, erastin treatment, cell death mode assays, iron and cystine uptake measurements, SLC7A11/GPX4 expression analysis Antioxidants (Basel, Switzerland) High 41596099
2025 Cold-induced accumulation of arachidonoyl-phosphatidylethanolamine (AA-PE) in brown adipose tissue mitochondria, driven by LPCAT3, partitions at the COX4I1 interface of the Cytochrome c oxidase complex, enhancing electron transport chain efficiency and thermogenesis. Lipid-based proteomics and molecular dynamics simulations identified this specific COX4I1-lipid interaction. Lipid-based proteomics, molecular dynamics simulations, bioenergetic analyses, fat-specific Lpcat3 knockout mice bioRxiv (preprint)preprint Medium bio_10.1101_2025.05.15.654206
2025 Functional studies in patient tissues and transiently transfected cell lines showed that COX4I1 pathogenic variants (deep intronic and nonsense) exert their effect primarily by reducing COX4I1 protein levels, thereby impairing proper assembly and activity of Complex IV. Proteomic data also implicated downstream effects on mitoribosomal protein levels. Patient fibroblast functional studies, transiently transfected cell lines, Complex IV activity assays, proteomic analysis of patient fibroblasts Mitochondrion Medium 41203052

Source papers

Stage 0 corpus · 33 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Repositioning chlorpromazine for treating chemoresistant glioma through the inhibition of cytochrome c oxidase bearing the COX4-1 regulatory subunit. Oncotarget 63 28455961
2015 Male obesity is associated with changed spermatozoa Cox4i1 mRNA level and altered seminal vesicle fluid composition in a mouse model. Molecular human reproduction 60 25731709
2017 Mutation in the COX4I1 gene is associated with short stature, poor weight gain and increased chromosomal breaks, simulating Fanconi anemia. European journal of human genetics : EJHG 47 28766551
2021 Loss of COX4I1 Leads to Combined Respiratory Chain Deficiency and Impaired Mitochondrial Protein Synthesis. Cells 45 33578848
1990 Isolation and characterization of QCR9, a nuclear gene encoding the 7.3-kDa subunit 9 of the Saccharomyces cerevisiae ubiquinol-cytochrome c oxidoreductase complex. An intron-containing gene with a conserved sequence occurring in the intron of COX4. The Journal of biological chemistry 43 2174427
2008 Noncovalent interactions under extreme conditions: high-pressure and low-temperature diffraction studies of the isostructural metal-organic networks (4-chloropyridinium)2[CoX4] (X = Cl, Br). Journal of the American Chemical Society 39 18564841
2007 The characterization and role of zinc binding in yeast Cox4. The Journal of biological chemistry 32 17215247
2020 Cytochrome C Oxidase Subunit 4 (COX4): A Potential Therapeutic Target for the Treatment of Medullary Thyroid Cancer. Cancers 26 32911610
2006 Translational regulation of nuclear gene COX4 expression by mitochondrial content of phosphatidylglycerol and cardiolipin in Saccharomyces cerevisiae. Molecular and cellular biology 25 16428432
2018 HIF-1α regulates COXIV subunits, a potential mechanism of self-protective response to microwave induced mitochondrial damages in neurons. Scientific reports 24 29991768
2009 Polyamine modulon in yeast-Stimulation of COX4 synthesis by spermidine at the level of translation. The international journal of biochemistry & cell biology 24 19695341
2019 Biallelic variants in COX4I1 associated with a novel phenotype resembling Leigh syndrome with developmental regression, intellectual disability, and seizures. American journal of medical genetics. Part A 20 31290619
1987 The untranslated leader of nuclear COX4 gene of Saccharomyces cerevisiae contains an intron. Nucleic acids research 20 3033605
2022 COX4-1 promotes mitochondrial supercomplex assembly and limits reactive oxide species production in radioresistant GBM. Cell stress 19 35478774
2020 COXIV and SIRT2-mediated G6PD deacetylation modulate ROS homeostasis to extend pupal lifespan. The FEBS journal 18 33058529
2020 The Dynll1-Cox4i1 Complex Regulates Intracellular Pathogen Clearance via Release of Mitochondrial Reactive Oxygen Species. Infection and immunity 16 32041786
2021 MicroRNA-338 inhibition protects against focal cerebral ischemia and preserves mitochondrial function in vitro in astrocytes and neurons via COX4I1. Mitochondrion 15 33933660
1999 The 5' region of the COX4 gene contains a novel overlapping gene, NOC4. Mammalian genome : official journal of the International Mammalian Genome Society 15 10337626
2010 The cardiac copper chaperone proteins Sco1 and CCS are up-regulated, but Cox 1 and Cox4 are down-regulated, by copper deficiency. Biological trace element research 14 20878365
2024 Cytochrome c oxidase IV isoform 1 (COX4-1) regulates the proliferation, migration and invasion of trophoblast cells via modulating mitochondrial function. Placenta 13 38718733
2022 COX4-like, a Nuclear-Encoded Mitochondrial Gene Duplicate, Is Essential for Male Fertility in Drosophila melanogaster. Genes 10 35327978
2022 Replicative Stress Coincides with Impaired Nuclear DNA Damage Response in COX4-1 Deficiency. International journal of molecular sciences 10 35456968
2022 Destabilizing COXIV in Müller Glia Increases Retinal Glycolysis and Alters Scotopic Electroretinogram. Cells 9 36497016
2017 Subfunctionalization of COX4 paralogs in fish. American journal of physiology. Regulatory, integrative and comparative physiology 9 28148493
2007 Leptin stimulation of COXIV is impaired in obese skeletal muscle myotubes. Obesity research & clinical practice 8 24351431
2024 Nuclear Control of Mitochondrial Homeostasis and Venetoclax Efficacy in AML via COX4I1. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 6 39716856
2018 Comparison of Pre- and Post-translational Expressions of COXIV-1 and MT-ATPase 6 Genes in Colorectal Adenoma-Carcinoma Tissues. Journal of carcinogenesis & mutagenesis 6 30393577
2016 Evaluating the role of NRF-1 in the regulation of the goldfish COX4-1 gene in response to temperature. The Journal of experimental biology 6 27471277
2025 Compound heterozygosity of a De novo 16q24.1 deletion and missense mutation in COX4I1 leads to developmental regression, intellectual disability, and seizures. Epilepsia open 2 40095452
2002 Cloning of COX4 cDNA from the NZ white rabbit and expression of this gene in bladder smooth muscle following partial outlet obstruction. World journal of urology 2 12215857
2025 The Nuclear-Encoded Cytochrome c Oxidase Subunit COX4-1 Enhances Hypoxia Tolerance in Glioblastoma Cells. Journal of oncology research and therapy 1 40958887
2025 Complex IV deficiency due to COX4I1 deep intronic and de novo variants results in progressive motor impairment and Leigh syndrome. Mitochondrion 1 41203052
2025 Cytochrome c Oxidase Subunit COX4-1 Reprograms Erastin-Induced Cell Death from Ferroptosis to Apoptosis: A Transmitochondrial Study. Antioxidants (Basel, Switzerland) 0 41596099

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