Affinage

Showing COXFA4L2 — NDUFA4L2 is a alias.

COXFA4L2

Cytochrome c oxidase hypoxia associated subunit FA4L2 · UniProt Q9NRX3

Length
87 aa
Mass
10.0 kDa
Annotated
2026-06-09
27 papers in source corpus 18 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COXFA4L2 (NDUFA4L2) is a nuclear-encoded mitochondrial protein that serves as a hypoxia-driven brake on oxidative metabolism, restraining electron transport chain activity to limit oxygen consumption and reactive oxygen species (ROS) production (PMID:22100406, PMID:35929074). Its expression is a direct transcriptional output of the HIF pathway: HIF-1α binds the hypoxia response element of the NDUFA4L2 promoter (PMID:29953852), and PHD2/PHD3-dependent HIF stabilization controls its constitutive, cell-type-restricted expression in brain pericytes and mural cells, where loss of the protein raises oxygen consumption and amplifies the cellular hypoxia response (PMID:35929074). Mechanistically, COXFA4L2 inhibits respiratory Complex I activity without altering ETC protein content, and its loss restores Complex I flux with consequent mitoROS accumulation and apoptosis (PMID:22100406, PMID:34724256, PMID:39154121). This metabolic restraint produces a Warburg-like shift toward glycolysis and reshapes mitochondrial dynamics, promoting mitochondrial fragmentation and mitochondrial–lysosomal associations (PMID:36722045). Across many disease settings the same ROS-suppressive function is co-opted: it confers cytoprotection in cardiomyocytes and cardiac stem cells under hypoxia/reperfusion (PMID:28429857, PMID:29953852), drives proliferation and vascular remodeling in pulmonary artery smooth muscle cells via a p38–5-lipoxygenase axis (PMID:33340241), promotes reactive gliosis through PI3K/AKT signaling in retinal Müller cells (PMID:42235340), and underlies tumor growth and resistance to multiple anticancer agents by suppressing ROS-mediated cell death (PMID:34276814, PMID:36369883, PMID:26819450). Beyond its respiratory inhibitory role, COXFA4L2 is a paralog of the Complex IV subunit COXFA4 (NDUFA4) and is upregulated to functionally compensate for COXFA4 loss, preserving residual cytochrome c oxidase activity in patient-derived fibroblasts from individuals with biallelic COXFA4-null Leigh-like encephalopathy (PMID:42218136).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2011 High

    Established the founding mechanism: how does a HIF target gene help cells survive hypoxia metabolically? COXFA4L2 was shown to inhibit Complex I, lowering O2 consumption and ROS.

    Evidence RNAi silencing and knockout MEFs with oxygen consumption and Complex I activity assays

    PMID:22100406

    Open questions at the time
    • Molecular basis of Complex I inhibition (binding site, stoichiometry) not defined
    • Does not address whether the protein associates with Complex I or acts indirectly
  2. 2016 Medium

    Tested whether the ROS-suppressive function is exploited by tumors; NDUFA4L2 inactivation raised mitochondrial activity, ROS, and apoptosis and impaired HCC growth/metastasis.

    Evidence siRNA knockdown, oxygen consumption/ROS/apoptosis assays, orthotopic HCC mouse model, HIF inhibitor

    PMID:26819450

    Open questions at the time
    • Direct molecular target within mitochondria not identified
    • Single lab
  3. 2018 Medium

    Resolved the direct transcriptional control: HIF-1α binds the NDUFA4L2 HRE to activate it, and this supports cell survival under hypoxia.

    Evidence ChIP for HIF-1α at the HRE, HIF agonist/inhibitor, siRNA knockdown and viability assays in cardiac stem cells

    PMID:29953852

    Open questions at the time
    • Does not address additional transcription factor inputs
    • Single lab
  4. 2017 Medium

    Probed cytoprotection mechanism in cardiomyocytes; overexpression prevented hypoxia/reperfusion apoptosis and mitochondrial dysfunction, with Complex I silencing recapitulating the effect to establish epistasis.

    Evidence Overexpression/knockdown in H9c2 cells with apoptosis, ATP, mPTP, and cytochrome c assays

    PMID:28429857

    Open questions at the time
    • No in vivo cardiac validation
    • Not independently replicated
  5. 2017 Low

    Began mapping upstream regulators beyond HIF; ELK1 was shown to positively regulate NDUFA4L2 in ccRCC.

    Evidence ELK1 knockdown with NDUFA4L2 readout and clinical correlation

    PMID:29158991

    Open questions at the time
    • Single knockdown experiment, single method
    • No direct promoter binding demonstrated
  6. 2019 Medium

    Extended the survival role to oxidative-stress contexts; NDUFA4L2 limits apoptosis by suppressing excessive mitophagy in nucleus pulposus cells.

    Evidence Primary NP cells, TBHP oxidative stress, mitophagy inhibitor rescue, gain/loss of function, in vivo IVDD model

    PMID:31740659

    Open questions at the time
    • Mechanistic link between Complex I inhibition and mitophagy regulation not defined
    • Single lab
  7. 2020 Medium

    Identified a downstream signaling consequence of NDUFA4L2-driven ROS; in PASMCs it engages a p38–5-lipoxygenase pathway and lipid peroxidation to drive proliferation and vascular remodeling.

    Evidence siRNA knockdown in human PASMCs, MDA/4-HNE/ROS assays, p38-5-LO western blots, hypoxic PAH rat model

    PMID:33340241

    Open questions at the time
    • How ROS selectively activates p38-5-LO unclear
    • Single lab
  8. 2021 Medium

    Demonstrated direct mitochondrial localization tied to function; NDUFA4L2 facilitates HER2 mitochondrial relocalization and suppresses ROS to drive trastuzumab resistance.

    Evidence Immunofluorescence and mitochondrial fractionation, Seahorse, DCFDA ROS, overexpression, resistance assays

    PMID:34276814

    Open questions at the time
    • Direct physical interaction with HER2 not established
    • Single lab
  9. 2021 High

    Provided in vivo gain-of-function evidence in skeletal muscle, linking metabolic restraint to muscle wasting; ectopic expression reduced respiration/ROS, depleted nucleotide pools, and caused muscle mass loss with atrogene/apoptotic gene induction.

    Evidence Adenoviral/electroporation expression in mouse muscle, femoral artery ligation, respiration and metabolite measurements, muscle force

    PMID:34724256

    Open questions at the time
    • Whether endogenous induction reaches pathogenic thresholds in disease unclear
    • Molecular trigger of atrogene program not defined
  10. 2021 Medium

    Connected NDUFA4L2 to the ccRCC phenotype in vivo; knockdown reduced renal lipid accumulation and ccRCC markers CA9 and ENO1.

    Evidence Dox-inducible shRNA knockdown in TRACK transgenic mouse kidney, lipid staining, marker quantification

    PMID:34970493

    Open questions at the time
    • Causal mechanism linking respiration inhibition to lipid deposition not resolved
    • Single genetic model
  11. 2022 High

    Defined cell-type-specific expression and its physiological coupling to hypoxia sensing; NDUFA4L2 is pericyte/mural-cell enriched, PHD2/3-HIF controlled, and tunes O2 consumption against the HIF response.

    Evidence scRNA-seq, multiplexed FISH, Ng2-cre Vhl conditional knockout, pericyte O2 consumption and HIF reporter assays

    PMID:35929074

    Open questions at the time
    • Physiological role in neurovascular function not directly tested
    • Does not address Complex I vs other respiratory targets in pericytes
  12. 2022 Medium

    Added transcriptional and post-translational regulators in cancer; NFIB binds the promoter to induce NDUFA4L2 (sorafenib resistance), and NXPH4 stabilizes the protein to drive glycolysis/ROS (gemcitabine resistance).

    Evidence Promoter binding assays, NFIB and NXPH4 knockdown with rescue, ROS/glycolysis assays, in vivo tumor models

    PMID:35954445 PMID:36369883

    Open questions at the time
    • Mechanism of NXPH4-mediated protein stabilization unknown
    • Direct vs indirect promoter binding by NFIB not fully resolved
  13. 2023 Medium

    Broadened the cellular role beyond Complex I; proteomics and imaging linked NDUFA4L2 to a Warburg-like shift, mitochondrial fragmentation, and mitochondrial-lysosomal associations including NPC1/NPC2.

    Evidence CRISPR KO (RCC4), co-IP MS proteomics, Seahorse, high-resolution live-cell microscopy

    PMID:36722045

    Open questions at the time
    • The very large co-IP interactome (3,215 proteins) lacks specificity filtering for direct partners
    • Functional significance of NPC1/NPC2 association not tested
  14. 2024 Medium

    Uncovered new downstream effector axes; miR-183-5p directly targets NDUFA4L2 to release Complex I and raise mitoROS in LUSC, and a NDUFA4L2→IL-33→PADI4/NET axis inhibits cuproptosis to drive lenvatinib resistance in HCC.

    Evidence miR overexpression/knockdown with Complex I and mitoROS assays; IL-33/NET/cuproptosis assays with mTOR and PADI4 inhibitors, in vivo HCC models

    PMID:39154121 PMID:39585643

    Open questions at the time
    • How NDUFA4L2 induces IL-33 production mechanistically unclear
    • Single lab for each axis
  15. 2026 High

    Revealed a distinct Complex IV role; as a COXFA4 paralog, COXFA4L2 is upregulated to compensate for COXFA4 loss and preserve COX activity in COXFA4-null patient cells.

    Evidence Patient-derived fibroblasts (13 individuals), COX activity and assembly assays, COXFA4L2 protein quantification

    PMID:42218136

    Open questions at the time
    • Whether COXFA4L2 is a constitutive Complex IV subunit or only a compensatory substitute unclear
    • Relationship between Complex I inhibitory and Complex IV roles not reconciled
  16. 2026 Medium

    Established a signaling output in retinal disease; Ndufa4l2 activates PI3K/AKT to drive Muller cell gliosis, proliferation, and migration under ischemia.

    Evidence scRNA-seq (OIR model), CRISPR KO/overexpression, PI3K inhibitor (LY294002) rescue, in vitro and in vivo validation

    PMID:42235340

    Open questions at the time
    • How a mitochondrial respiratory regulator activates PI3K/AKT not defined
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural and biochemical basis by which COXFA4L2 inhibits Complex I versus functions at Complex IV remains unresolved, as does how a single mitochondrial protein produces such diverse downstream signaling (PI3K/AKT, p38-5-LO, IL-33/NET) outputs.
  • No structure or direct binding partner within Complex I established
  • Whether respiratory inhibition and Complex IV compensation are the same protein pool unknown
  • Mechanism linking metabolic restraint to specific cytoplasmic signaling cascades unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0005198 structural molecule activity 1
Localization
GO:0005739 mitochondrion 3
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-1643685 Disease 3 R-HSA-8953897 Cellular responses to stimuli 2
Partners
COXFA4HER2NPC1NPC2NXPH4
Complex memberships
Cytochrome c oxidase / Complex IV (compensatory subunit)Mitochondrial respiratory Complex I (inhibitory regulator)

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 NDUFA4L2 (COXFA4L2) is a HIF-1α target gene whose hypoxia-induced expression attenuates mitochondrial oxygen consumption by inhibiting Complex I activity, thereby limiting intracellular ROS production under low-oxygen conditions. This was demonstrated using NDUFA4L2-silenced cells and NDUFA4L2 knockout murine embryonic fibroblasts. RNAi silencing, NDUFA4L2 knockout MEFs, oxygen consumption assays, Complex I activity assay Cell Metabolism High 22100406
2017 NDUFA4L2 overexpression in H9c2 cardiomyocytes subjected to hypoxia/reperfusion prevents apoptosis and mitochondrial dysfunction (increased ATP, delayed mPTP opening, reduced cytochrome c release) via inhibition of Complex I activity; silencing Complex I itself recapitulates the cardioprotective effect. Overexpression and knockdown in H9c2 cells, flow cytometry apoptosis, western blot (Bax/Bcl-2), ATP measurement, mPTP opening assay, cytochrome c detection Clinical and Experimental Pharmacology & Physiology Medium 28429857
2018 HIF-1α directly binds the hypoxia response element (HRE) of the NDUFA4L2 promoter to transcriptionally activate NDUFA4L2 in cardiac stem cells, and this signaling promotes CSC survival under hypoxia; knockdown of NDUFA4L2 reverses the survival benefit. ChIP assay (HIF-1α binding to NDUFA4L2 HRE), HIF-1α agonist/inhibitor (DMOG/2-ME) treatment, NDUFA4L2 siRNA knockdown, cell viability assay Biochemical and Biophysical Research Communications Medium 29953852
2019 NDUFA4L2 attenuates apoptosis of nucleus pulposus cells under oxidative stress by suppressing excessive mitophagy; TBHP-induced oxidative stress decreases HIF-1α/NDUFA4L2 signaling to promote mitophagy and apoptosis, whereas NDUFA4L2 upregulation blocks this pathway. Primary human NP cell culture, TBHP oxidative stress model, mitophagy inhibitor rescue, NDUFA4L2 overexpression/knockdown, flow cytometry apoptosis, in vivo IVDD model Experimental & Molecular Medicine Medium 31740659
2021 Ectopic NDUFA4L2 expression in mouse skeletal muscle reduces mitochondrial respiration and ROS production, lowers AMP, ADP, ATP, and NAD+ levels without altering ETC protein content, causes ~20% reduction in muscle mass, and induces atrogene (MuRF1, Mul1) and apoptotic gene (caspase 3, Bax) expression; femoral artery ligation induces endogenous NDUFA4L2 and its expression correlates with reduced muscle force. Adenovirus-mediated ectopic NDUFA4L2 expression in vivo, in vivo electroporation, femoral artery ligation model, mitochondrial respiration assay, metabolite quantification (AMP/ADP/ATP/NAD+), muscle mass and force measurements, gene expression analysis FASEB Journal High 34724256
2021 NDUFA4L2 overexpression in HER2-positive breast cancer cells facilitates mitochondrial relocalization of HER2 and suppresses ROS production, thereby promoting trastuzumab resistance; mitochondrial localization of NDUFA4L2 was confirmed by immunofluorescence and subcellular fractionation western blot. Immunofluorescence and mitochondrial fractionation western blot (localization), Seahorse metabolic assay, DCFDA ROS measurement, NDUFA4L2 overexpression, trastuzumab resistance assay Therapeutic Advances in Medical Oncology Medium 34276814
2022 NFIB transcription factor binds to the promoter region of NDUFA4L2 and promotes its transcription in hepatocellular carcinoma cells; this transcriptional upregulation of NDUFA4L2 inhibits sorafenib-induced ROS accumulation, driving sorafenib resistance. Gene expression profiling, promoter binding assay (NFIB binding to NDUFA4L2 promoter), NFIB knockdown, NDUFA4L2 expression measurement, ROS assay, in vitro and in vivo tumor models Cancer Science Medium 36369883
2022 In mouse and human brain, NDUFA4L2 is constitutively and specifically expressed in pericytes (highest) and mural cells; its expression is regulated by PHD2/PHD3-dependent HIF stabilization (Vhl conditional knockout dramatically induces expression). NDUFA4L2 inactivation in pericytes increases oxygen consumption and enhances HIF pathway induction under hypoxia, establishing that NDUFA4L2 couples mitochondrial O2 consumption to the cellular hypoxia response in pericytes. scRNA-seq analysis, multiplexed fluorescence RNA in situ hybridization, Ng2-cre Vhl conditional knockout mice, in vitro human brain pericyte culture, oxygen consumption assay, HIF pathway reporter readout Journal of Cerebral Blood Flow and Metabolism High 35929074
2022 NXPH4 promotes stability of NDUFA4L2 protein in bladder cancer cells; increased NDUFA4L2 levels downstream of NXPH4 activate ROS and glycolysis, contributing to gemcitabine resistance. Rescue experiments show NDUFA4L2 is required for NXPH4-regulated functions. Rescue assays (NDUFA4L2 re-expression in NXPH4-knockdown cells), glycolytic activity assay, ROS measurement, in vivo xenograft validation Cancers Medium 35954445
2023 NDUFA4L2 expression in ccRCC cells induces a Warburg-like metabolic shift (increased extracellular acidification rate, decreased oxygen consumption rate). Mass-spectrometry-based proteomics of NDUFA4L2-associated complexes identified 3,215 co-immunoprecipitated proteins, with top pathways including 'Metabolic Reprogramming in Cancer' and 'Warburg Effect.' NDUFA4L2 enhances mitochondrial fragmentation and increases mitochondrial-lysosomal associations; 161 lysosomal proteins including NPC1 and NPC2 associate with NDUFA4L2, and NDUFA4L2 regulates lysosomal size and abundance. CRISPR-Cas9 NDUFA4L2 knockout (RCC4-KO), MS-based proteomics of immunoprecipitated NDUFA4L2 complexes, Seahorse metabolic assay, high-resolution fluorescence microscopy and live cell imaging Cancer Biology & Therapy Medium 36722045
2024 Lenvatinib increases NDUFA4L2 expression in HCC cells, leading to increased IL-33 production and secretion; IL-33 triggers neutrophil extracellular trap (NET) formation via Akt/mTOR-dependent PADI4 upregulation. This NDUFA4L2→IL-33→PADI4/NET axis inhibits cuproptosis in HCC cells and drives lenvatinib resistance. NDUFA4L2 expression manipulation in HCC cells, IL-33 knockdown, NETs measurement (CitH3, MPO-DNA, elastase, MPO activity), cuproptosis assay (copper content, FDX1, pyruvate), in vivo HCC mouse models, mTOR inhibitor (rapamycin) and PADI4 inhibitor (GSK484) Cellular Oncology Medium 39585643
2024 miR-183-5p directly targets NDUFA4L2 mRNA and negatively regulates its expression; this reduces NDUFA4L2-mediated suppression of mitochondrial Complex I activity, leading to mitoROS accumulation and suppression of lung squamous cell carcinoma cell survival in vitro and in vivo. miR-183-5p overexpression, NDUFA4L2 knockdown, mitoROS measurement, Complex I activity assay, apoptosis assay, in vivo xenograft model Oncogene Medium 39154121
2026 COXFA4L2 is a paralog of COXFA4 (formerly NDUFA4), a nuclear-encoded cytochrome c oxidase (Complex IV) subunit. In patient-derived fibroblasts from individuals with biallelic COXFA4-null variants (Leigh-like encephalopathy), COXFA4L2 is upregulated and compensates for loss of COXFA4, preserving residual COX activity; this identifies a paralog-mediated compensatory mechanism at Complex IV. Patient-derived fibroblast studies (13 individuals, 12 families), COX activity assay, COXFA4L2 protein quantification, COX assembly analysis Nature Communications High 42218136
2026 Ndufa4l2 activates the PI3K/AKT signaling pathway in retinal Müller cells under ischemic/hypoxic stress, driving reactive gliosis, hyper-proliferation, and enhanced migration; pharmacological PI3K inhibition (LY294002) reverses these Ndufa4l2-induced effects. scRNA-seq (OIR mouse model), CRISPR/Cas9 knockout and overexpression of Ndufa4l2, bioinformatics pathway analysis, PI3K inhibitor (LY294002) rescue experiments, in vitro and in vivo validation Pathology, Research and Practice Medium 42235340
2016 NDUFA4L2 is HIF-1-regulated in HCC cells; inactivation of NDUFA4L2 increases mitochondrial activity and oxygen consumption, resulting in ROS accumulation and apoptosis. Knockdown of NDUFA4L2 suppresses HCC growth and metastasis in an orthotopic in vivo model. NDUFA4L2 knockdown (siRNA), oxygen consumption measurement, ROS assay, apoptosis assay, orthotopic HCC mouse model, HIF inhibitor (digoxin) treatment Clinical Cancer Research Medium 26819450
2017 ELK1 transcription factor positively regulates NDUFA4L2 expression in ccRCC cells; ELK1 knockdown reduces NDUFA4L2 expression, and ELK1 levels positively correlate with NDUFA4L2 in ccRCC clinical tissues. ELK1 knockdown in ccRCC cells, NDUFA4L2 expression measurement by western blot/qPCR, correlation analysis in clinical samples PeerJ Low 29158991
2020 In hypoxic pulmonary artery smooth muscle cells, NDUFA4L2 (downstream of HIF-1α) promotes ROS-mediated lipid peroxidation (MDA and 4-HNE accumulation) and activates a p38–5-lipoxygenase downstream signaling pathway to drive PASMC proliferation and vascular remodeling; siNDUFA4L2 blocks these effects. NDUFA4L2 siRNA knockdown in human PASMCs, MDA/4-HNE measurement, ROS assay, 5-LO/p38 pathway western blot, in vivo hypoxic PAH rat model Journal of Cellular and Molecular Medicine Medium 33340241
2021 Ndufa4l2 knockdown in renal proximal tubules of a TRACK mouse model reduces neutral lipid accumulation and decreases expression of ccRCC markers carbonic anhydrase 9 (CA9) and Enolase 1 (ENO1), linking mitochondrial NDUFA4L2 to lipid deposition and ccRCC marker expression. Dox-inducible shRNA-mediated knockdown of Ndufa4l2 in transgenic mouse kidney (TRACK model), lipid staining, CA9 and ENO1 protein quantification Frontiers in Oncology Medium 34970493

Source papers

Stage 0 corpus · 27 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Induction of the mitochondrial NDUFA4L2 protein by HIF-1α decreases oxygen consumption by inhibiting Complex I activity. Cell metabolism 309 22100406
2018 Integrated multi-omics characterization reveals a distinctive metabolic signature and the role of NDUFA4L2 in promoting angiogenesis, chemoresistance, and mitochondrial dysfunction in clear cell renal cell carcinoma. Aging 193 30538212
2019 Mitochondrial NDUFA4L2 attenuates the apoptosis of nucleus pulposus cells induced by oxidative stress via the inhibition of mitophagy. Experimental & molecular medicine 98 31740659
2016 NDUFA4L2 Fine-tunes Oxidative Stress in Hepatocellular Carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 77 26819450
2020 NDUFA4L2 Regulated by HIF-1α Promotes Metastasis and Epithelial-Mesenchymal Transition of Osteosarcoma Cells Through Inhibiting ROS Production. Frontiers in cell and developmental biology 33 33330441
2019 Mitochondrial NDUFA4L2 protein promotes the vitality of lung cancer cells by repressing oxidative stress. Thoracic cancer 32 30710412
2020 NDUFA4L2 in smooth muscle promotes vascular remodeling in hypoxic pulmonary arterial hypertension. Journal of cellular and molecular medicine 26 33340241
2017 NDUFA4L2 is associated with clear cell renal cell carcinoma malignancy and is regulated by ELK1. PeerJ 26 29158991
2022 NXPH4 Promotes Gemcitabine Resistance in Bladder Cancer by Enhancing Reactive Oxygen Species and Glycolysis Activation through Modulating NDUFA4L2. Cancers 22 35954445
2021 NDUFA4L2 promotes trastuzumab resistance in HER2-positive breast cancer. Therapeutic advances in medical oncology 22 34276814
2022 Transcriptional regulation of NDUFA4L2 by NFIB induces sorafenib resistance by decreasing reactive oxygen species in hepatocellular carcinoma. Cancer science 20 36369883
2021 Mitochondrial NDUFA4L2 is a novel regulator of skeletal muscle mass and force. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18 34724256
2024 Lenvatinib-activated NDUFA4L2/IL33/PADI4 pathway induces neutrophil extracellular traps that inhibit cuproptosis in hepatocellular carcinoma. Cellular oncology (Dordrecht, Netherlands) 17 39585643
2023 NDUFA4L2 reduces mitochondrial respiration resulting in defective lysosomal trafficking in clear cell renal cell carcinoma. Cancer biology & therapy 15 36722045
2018 Induction of the mitochondrial NDUFA4L2 protein by HIF-1a regulates heart regeneration by promoting the survival of cardiac stem cell. Biochemical and biophysical research communications 14 29953852
2021 Mitochondrial Ndufa4l2 Enhances Deposition of Lipids and Expression of Ca9 in the TRACK Model of Early Clear Cell Renal Cell Carcinoma. Frontiers in oncology 13 34970493
2017 NDUFA4L2 protects against ischaemia/reperfusion-induced cardiomyocyte apoptosis and mitochondrial dysfunction by inhibiting complex I. Clinical and experimental pharmacology & physiology 12 28429857
2022 Unique expression of the atypical mitochondrial subunit NDUFA4L2 in cerebral pericytes fine tunes HIF activity in response to hypoxia. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 9 35929074
2023 Hypoxia-induced the upregulation of NDUFA4L2 promoted colon adenocarcinoma progression through ROS-mediated PI3K/AKT pathway. Cytotechnology 8 37841958
2025 Nucleotide metabolism-associated drug resistance gene NDUFA4L2 promotes colon cancer progression and 5-FU resistance. Scientific reports 4 39747340
2024 MiR-183-5p inhibits lung squamous cell carcinoma survival through disrupting hypoxia adaptation mediated by HIF-1α/NDUFA4L2 axis. Oncogene 4 39154121
2025 A multidimensional pan-cancer analysis of NDUFA4L2 and verification of the oncogenic value in colon cancer. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2 39792315
2024 Pancancer analysis of NDUFA4L2 with focused role in tumor progression and metastasis of colon adenocarcinoma. Medical oncology (Northwood, London, England) 1 39402288
2026 NDUFA4L2 regulates the progression and chemotherapy sensitivity of HNSCC by inhibiting PANoptosis. NPJ precision oncology 0 41787028
2026 COXFA4L2 upregulation preserves residual cytochrome c oxidase activity in COXFA4-related Leigh-like encephalopathy. Nature communications 0 42218136
2026 Ndufa4l2 drives the pathological activation of Müller cells in ischemic retinopathy via the PI3K/AKT signaling pathway. Pathology, research and practice 0 42235340
2024 Letter to the editor: the potential value of NDUFA4L2 in colon adenocarcinoma remains to be fully evaluated. Medical oncology (Northwood, London, England) 0 39570435

Missed literature

Know a paper Affinage missed for COXFA4L2? Flag it for the maintainers and the community.

No submissions yet.