Affinage

Showing PRDX3 — AOP-1 is a alias.

PRDX3

Thioredoxin-dependent peroxide reductase, mitochondrial · UniProt P30048

Length
256 aa
Mass
27.7 kDa
Annotated
2026-06-10
78 papers in source corpus 27 papers cited in narrative 27 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

PRDX3 is a mitochondria-localized 2-Cys peroxiredoxin that serves as a primary thioredoxin-dependent scavenger of hydrogen peroxide and organic hydroperoxides in the mitochondrial compartment (PMID:9363753, PMID:12773537). It assembles into a stable decameric toroid of five dimeric units linked by intermolecular disulfides between the catalytic Cys-47 of one subunit and Cys-168 of its neighbor, with Cys-47 being essential for peroxidase activity (PMID:12773537); catalytic turnover is driven by the mitochondrial thioredoxin/thioredoxin-reductase/NADPH system (PMID:9363753). The protein is dually targeted within mitochondria, processed into the matrix by MPP and MIP and sorted to the intermembrane space via the IMP complex (PMID:39591905). Through this peroxidase activity PRDX3 protects mitochondrial macromolecules from oxidative damage in vivo, limiting ROS accumulation, protein carbonylation and DNA oxidation, and conferring tolerance to oxidative stress (PMID:9890990, PMID:17316558); it preserves mitochondrial mass, membrane potential and ATP output, and protects mtDNA in part by shielding the uracil-DNA glycosylase UNG1 from LonP1-mediated degradation through a redox-dependent disulfide interaction (PMID:12011429, PMID:27480846, PMID:41147088). PRDX3 expression and abundance are tightly controlled: it is a direct transcriptional target of c-Myc and is required for Myc-driven proliferation and transformation (PMID:12011429), and its translation is governed by YTHDF3 reading of m6A-modified PRDX3 mRNA (PMID:35779442). Its activity and stability are set by a dense layer of post-translational modifications—SIRT3- and SIRT4-mediated deacetylation at K253 and K92 (activating and dimerization-promoting) (PMID:31655428, PMID:40765819), KAT2A succinylation at K84 (destabilizing) (PMID:40457625), PPT1-mediated depalmitoylation of the catalytic C108 (activating) (PMID:41865945), TRIM39-driven K48-linked ubiquitination at K73/K149 (degrading) (PMID:38195664), and SUMOylation suppressed by ERβ (PMID:38097136). During ferroptosis, mitochondrial lipid peroxides hyperoxidize the catalytic cysteine to sulfinic/sulfonic acid, triggering PRDX3 translocation from mitochondria to the plasma membrane where it inhibits cystine uptake and promotes cell death (PMID:37863053). PRDX3 also sustains PINK1/Parkin-dependent mitophagy (PMID:39983849, PMID:40912394) and binds partner proteins including cyclophilin 18, which stimulates its activity, and the kinase TNNI3K, which it inhibits (PMID:9545370, PMID:18205602). Biallelic loss-of-function mutations in PRDX3 cause human cerebellar ataxia, with patient cells showing reduced glutathione peroxidase activity and impaired mitochondrial respiration (PMID:33889951).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1995 Medium

    Established that the then-named SP-22 protein had intrinsic radical-scavenging and protein-protective activity, the first functional clue to an antioxidant role.

    Evidence In vitro radical scavenging and protection assays with purified protein in adrenal cortex mitochondria

    PMID:7654218

    Open questions at the time
    • Did not define the catalytic mechanism or cofactor dependence
    • No identification of the physiological reducing system
  2. 1997 High

    Defined PRDX3 as a thioredoxin-dependent peroxide reductase, resolving how it catalytically reduces peroxides rather than acting as a passive scavenger.

    Evidence In vitro reconstitution with purified SP-22, mt-Trx, thioredoxin reductase and NADPH, with stoichiometric substrate consumption

    PMID:9363753

    Open questions at the time
    • Structural basis of catalysis not addressed
    • Catalytic residue identity not yet mapped
  3. 2003 High

    Defined the quaternary structure and catalytic residue, establishing PRDX3 as a decameric 2-Cys peroxiredoxin with Cys-47 as the active site.

    Evidence Recombinant expression, cysteine-to-serine mutagenesis (C47S, C66S, C168S), activity assays and electron microscopy

    PMID:12773537

    Open questions at the time
    • Did not address regulation of the oligomeric state in cells
    • Role of hyperoxidation not yet examined
  4. 2002 High

    Placed PRDX3 downstream of an oncogenic transcription factor by showing it is a direct c-Myc target required for transformation and mitochondrial maintenance.

    Evidence ChIP, mycER inducible system, c-myc-/- cells, mitochondrial mass/potential probes and loss-of-function assays

    PMID:12011429

    Open questions at the time
    • Mechanism linking peroxidase activity to proliferation not dissected
    • No direct measure of mitochondrial H2O2 flux
  5. 2007 High

    Confirmed PRDX3 as a physiologically important ROS scavenger in vivo and defined its mitochondrial localization and stress-inducibility.

    Evidence Germline KO mouse with LPS lung injury, oxidative damage readouts (8-OHdG, carbonylation); immunofluorescence localization in lens epithelium

    PMID:17316558 PMID:17893648 PMID:9890990

    Open questions at the time
    • Tissue-specific roles not separated
    • Upstream H2O2-sensing induction mechanism undefined
  6. 2007 Medium

    Identified protein partners that modulate PRDX3 activity, expanding its role beyond peroxide reduction to regulation of partner enzymes.

    Evidence Yeast two-hybrid, in vitro binding and kinase assays (TNNI3K); binding and activity-stimulation assays (cyclophilin 18)

    PMID:18205602 PMID:9545370

    Open questions at the time
    • Physiological context of TNNI3K inhibition not established
    • Structural basis of cyclophilin 18 stimulation unknown
  7. 2016 Medium

    Connected PRDX3 to mtDNA integrity and mitochondrial energetics, showing it protects UNG1 from protease degradation and supports ATP synthesis.

    Evidence Stable knockdown, proteomics, ATP/invasion assays in HepG2; redox-dependent disulfide Co-IP with UNG1 and LonP1 analysis

    PMID:26983019 PMID:27480846

    Open questions at the time
    • Reciprocal validation of UNG1 interaction limited
    • Causality between mtDNA protection and growth phenotype incomplete
  8. 2024 High

    Resolved PRDX3 biogenesis, establishing dual submitochondrial targeting to matrix and IMS via distinct processing pathways.

    Evidence Subfractionation with markers, carbonate extraction, in organello import and heterologous yeast expression

    PMID:39591905

    Open questions at the time
    • Functional difference between matrix and IMS pools unknown
    • Regulation of sorting choice undefined
  9. 2020 High

    Defined a layer of activity control via reversible acetylation, showing SIRT3 deacetylation of K253 promotes dimerization and protects against hyperoxidation.

    Evidence SIRT3 KD/KO, K253R/K253Q mutagenesis, dimerization and apoptosis readouts, I/R models; SIRT3-PRDX3 Co-IP in beta cells

    PMID:31655428 PMID:32763411

    Open questions at the time
    • Stoichiometry of endogenous acetylation unknown
    • Whether deacetylation directly versus indirectly affects catalysis unresolved
  10. 2021 High

    Established PRDX3 as a Mendelian disease gene, linking loss of its peroxidase function to human cerebellar ataxia and mitochondrial respiratory failure.

    Evidence Whole-exome sequencing across five families, patient fibroblast GPx and respirometry assays, tumor cell KD, Drosophila neuronal/glial models

    PMID:33889951 PMID:35766882

    Open questions at the time
    • Tissue selectivity of cerebellar phenotype unexplained
    • Genotype-phenotype correlation across mutations incomplete
  11. 2022 Medium

    Showed PRDX3 abundance is set translationally through m6A reading, adding RNA-level control to its known transcriptional regulation.

    Evidence RNA pull-down/MS, YTHDF1/2/3 KD comparison, m6A-dependent translation assays, hepatic stellate cell and in vivo AAV9 models

    PMID:35779442

    Open questions at the time
    • m6A site mapping on PRDX3 mRNA not detailed
    • Single-lab finding
  12. 2023 High

    Reframed PRDX3 as an active participant in ferroptosis, showing catalytic-cysteine hyperoxidation drives mitochondria-to-plasma-membrane translocation that inhibits cystine uptake.

    Evidence Ferroptosis assays, SO2/3-PRDX3 detection, subcellular fractionation, cystine uptake assay, fatty liver disease mouse models

    PMID:37863053

    Open questions at the time
    • Mechanism of membrane translocation and targeting undefined
    • How membrane PRDX3 inhibits the cystine transporter unresolved
  13. 2024 Medium

    Defined ubiquitin- and mitophagy-coupled regulation, identifying TRIM39 as a degrading E3 ligase and PINK1 as a partner sustaining mitophagic flux.

    Evidence Co-IP, K48 ubiquitination site mapping (K73/K149) with renal fibrosis model; PINK1 Co-IP and KD with mitophagy readouts in diabetic nephropathy and NPC models

    PMID:38195664 PMID:39983849 PMID:40912394

    Open questions at the time
    • Direct versus indirect PINK1 stabilization unresolved
    • Single-lab findings without reciprocal cross-validation
  14. 2025 Medium

    Extended PTM control to succinylation, depalmitoylation, second deacetylation site and SUMOylation, each tuning PRDX3 stability or activity in disease contexts.

    Evidence Co-IP and site mapping for KAT2A-K84, PPT1-C108, SIRT4-K92, ERβ-suppressed SUMOylation, with KO/OE and pharmacological models; Prdx3/Prdx5 double-KO muscle aging study

    PMID:38097136 PMID:40457625 PMID:40765819 PMID:41147088 PMID:41865945

    Open questions at the time
    • Cross-talk and hierarchy among the many PTMs unmapped
    • Each modification characterized in a single disease context

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the dense PTM network, dual submitochondrial localization, and ferroptotic translocation are integrated to set PRDX3 output under specific physiological conditions remains unresolved.
  • No unified model of PTM hierarchy and crosstalk
  • Functional distinction between matrix and IMS pools unknown
  • Structural basis of hyperoxidation-triggered translocation undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016209 antioxidant activity 4 GO:0016491 oxidoreductase activity 3 GO:0140098 catalytic activity, acting on RNA 2 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005739 mitochondrion 4 GO:0005886 plasma membrane 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-9612973 Autophagy 2
Partners
KAT2APINK1PPT1SIRT3SIRT4TNNI3KTRIM39UNG1

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 SP-22 (PRDX3) has radical scavenging activity, protecting radical-sensitive proteins (tryptophan hydroxylase, glutamine synthetase, hemoglobin) from oxidative damage; the protecting activity was enhanced by serum factor(s), consistent with its function as a substrate of mitochondrial ATP-dependent protease in adrenal cortex mitochondria. In vitro radical scavenging assay with Fe2+/dithiothreitol radical-generating system; biochemical protection assays with purified protein Biochemical and biophysical research communications Medium 7654218
1997 SP-22 (PRDX3) functions as a thioredoxin-dependent peroxide reductase in mitochondria: in the presence of mitochondrial thioredoxin (mt-Trx), a partially purified thioredoxin reductase (NADPH-dependent Nbs2 reductase), and NADPH, SP-22 catalyzes the stoichiometric reduction of H2O2 and tert-butyl hydroperoxide with concomitant NADPH oxidation. In vitro reconstitution assay with purified/partially purified SP-22, mt-Trx, Nbs2 reductase, and NADPH; NADPH oxidation monitored concomitant with H2O2 disappearance; functional protection of oxyhemoglobin from ascorbate-induced damage European journal of biochemistry High 9363753
1998 Human T cell cyclophilin 18 (hCyP18) directly binds to PRDX3 (Aop1) and stimulates its enzymatic antioxidant activity; the interaction is specific, as other PPIases do not stimulate Aop1 activity. Protein-protein interaction assay (binding confirmed); enzymatic activity stimulation assay with hCyP18 and other PPIases as controls Journal of molecular biology Medium 9545370
1999 SP-22 (PRDX3) functions as a mitochondrial antioxidant in cardiovascular endothelial cells: its expression is induced by oxidative stresses (including mitochondrial respiratory inhibitors that increase superoxide), and cells pre-treated with mild oxidative stress to increase SP-22 become tolerant to subsequent intense oxidative stress, while cells depleted of SP-22 by antisense oligodeoxynucleotide become more labile to oxidative stress. Antisense oligodeoxynucleotide knockdown in bovine aortic endothelial cells; oxidative stress tolerance assays; SP-22 induction by respiratory inhibitors (antimycin A); in vivo induction in rat myocardial infarction model The Journal of biological chemistry High 9890990
2002 PRDX3 is a transcriptional target of c-Myc: Myc binds preferentially to a ~930-bp region surrounding PRDX3 exon 1 (by ChIP), PRDX3 expression is induced by the mycER system and reduced in c-myc-/- cells, and PRDX3 is required for Myc-mediated proliferation, transformation, and apoptosis after glucose withdrawal. PRDX3 is also essential for maintaining mitochondrial mass and membrane potential in transformed cells. Chromatin immunoprecipitation (ChIP) across entire PRDX3 genomic sequence; mycER inducible system; c-myc-/- cell lines; fluorescent mitochondrial probes (mass and membrane potential); loss-of-function proliferation and transformation assays Proceedings of the National Academy of Sciences of the United States of America High 12011429
2003 Bovine mitochondrial SP-22 (PRDX3) is a 2-Cys peroxiredoxin that forms a stable decameric toroid of five basic dimeric units with intermolecular disulfide bonds linking catalytic Cys-47 of one subunit to Cys-168 of the adjacent monomer; Cys-47 is the catalytic residue (confirmed by C47S mutagenesis abolishing activity), while Cys-66 and Cys-168 are non-catalytic. The disulfide bonds are not required for overall structural integrity. Overexpression in E. coli; cysteine-to-serine mutagenesis (C47S, C66S, C168S); peroxidase activity assays; electron microscopy structural analysis of purified recombinant protein The Journal of biological chemistry High 12773537
2007 MER5/PRDX3 knockout mice accumulate significantly higher intracellular ROS levels in macrophages under basal conditions, and exhibit more severe LPS-induced lung injury (inflammatory cell infiltration, airway wall thickening, DNA oxidation as 8-OHdG, protein carbonylation) than wild-type mice, establishing PRDX3 as an important ROS scavenger in vivo. Germline knockout mouse model; intratracheal LPS inoculation; intracellular ROS measurement; 8-OHdG assay; protein carbonylation assay; histological analysis Biochemical and biophysical research communications High 17316558
2007 PRDX3 is localized to the mitochondria in human lens epithelial cells and is specifically induced by low levels of H2O2 (as little as 2 µM) but not by TBHP or heat-shock, suggesting a specific H2O2-sensing induction mechanism in the lens. Immunofluorescence (mitochondrial co-localization); RT-PCR; Western blot; H2O2, TBHP, and heat-treatment comparisons in human lens epithelial cells and rat lenses Molecular vision Medium 17893648
2007 PRDX3 (AOP-1) directly interacts with cardiac troponin I-interacting kinase TNNI3K via TNNI3K's ANK motif, confirmed by yeast two-hybrid, in vitro binding assay, co-expression in vivo, and confocal immunofluorescence co-localization; co-expression of AOP-1 inhibits TNNI3K kinase activity in an in vitro kinase assay. Yeast two-hybrid screening of adult heart cDNA library; in vitro binding assay; co-expression in vivo; confocal immunofluorescence co-localization; in vitro kinase assay Biochemistry. Biokhimiia Medium 18205602
2012 Drosophila Prx3 (ortholog of human PRDX3) is required for oxidative stress resistance in adult flies: RNAi-mediated knockdown does not change phenotype under normal conditions but results in shorter survival in the presence of H2O2; Prx3 expression levels decline with aging, linking PRDX3 to age-dependent oxidative stress competence. RNAi-induced knockdown in Drosophila; H2O2 survival assay; expression level analysis across ages Biomedical research (Tokyo, Japan) Medium 23124252
2016 PRDX3 knockdown in HepG2 hepatocellular carcinoma cells increases mtDNA oxidation, decreases ATP synthase expression and cellular ATP levels (slowing growth), and enhances invasive properties via TIMP-1 down-regulation and increased ECM degradation. Stable PRDX3 knockdown cell lines; quantitative proteomics (differentially expressed proteins); cellular ATP measurement; invasion assays; TIMP-1 expression analysis Journal of proteome research Medium 26983019
2016 Under oxidative stress (H2O2), PRDX3 interacts with UNG1 (mitochondrial uracil-DNA glycosylase isoform 1) via a disulfide linkage; this interaction protects UNG1 from ROS-mediated degradation by Lon protease 1 (LonP1) and prevents mtDNA oxidation. PRDX3 knockdown aggravates LonP1-dependent UNG1 degradation and mtDNA oxidation. Co-immunoprecipitation/proteomics under oxidative stress; disulfide linkage characterization; PRDX3 knockdown; Lon protease 1 interaction; mtDNA oxidation assay Free radical biology & medicine Medium 27480846
2019 SIRT3 deacetylates PRDX3 at lysine K253; acetylation of PRDX3 (increased by SIRT3 knockdown or sirtuin inhibition with nicotinamide) impairs its antioxidative activity and dimerization. The K253R (deacetylation-mimetic) mutation increases PRDX3 dimerization and protects against mitochondrial oxidative damage and apoptosis in I/R conditions, while K253Q (acetylation-mimetic) abolishes protection. SIRT3 knockdown; nicotinamide sirtuin inhibition; immunoprecipitation to identify acetylation site; K253R and K253Q mutagenesis; dimerization assay; mitochondrial damage and apoptosis readouts in vitro and in SIRT3 KO mice; intestinal I/R model Redox biology High 31655428
2020 Under high glucose conditions, PRDX3 is acetylated (mediated via SIRT1 degradation leading to SIRT3 inactivation), which promotes PRDX3 hyperoxidation, mitochondrial dysfunction, and beta-cell apoptosis via NOX-JNK-p66Shc signalosome activation; SIRT3 physically interacts with PRDX3 and deacetylates it, protecting against hyperoxidation. Co-immunoprecipitation (SIRT3-PRDX3 physical interaction); SIRT1 siRNA knockdown and inhibitor (EX-527); acetylation and hyperoxidation assays; apoptosis assays in INS-1 and 1.1B4 cells Free radical biology & medicine Medium 32763411
2021 Biallelic loss-of-function mutations in PRDX3 cause cerebellar ataxia in humans; patient fibroblasts lacking PRDX3 show decreased glutathione peroxidase activity and decreased mitochondrial maximal respiratory capacity; PRDX3 knockdown in cerebellar medulloblastoma cells reduces cell viability, increases H2O2 levels, and increases susceptibility to ROS-triggered apoptosis; pan-neuronal/pan-glial Drosophila KD models show aberrant locomotor phenotypes and reduced survival under oxidative stress. Whole-exome sequencing; patient fibroblast functional assays (glutathione peroxidase activity, Seahorse respirometry); siRNA knockdown in tumor cells; in vivo Drosophila neuronal/glial KD models Brain : a journal of neurology High 33889951
2022 PRDX3 mRNA is modified by m6A and specifically interacts with m6A reader YTHDF3 (but not YTHDF1 or YTHDF2); YTHDF3 knockdown suppresses PRDX3 expression at the translational level in an m6A-dependent manner, affecting PRDX3-mediated suppression of HSC activation via the mitochondrial ROS/TGF-β1/Smad2/3 pathway. RNA pull-down/mass spectrometry; m6A modification assay; YTHDF1/2/3 knockdown experiments; m6A-dependent translation assay; hepatic stellate cell activation assays; AAV9-mediated in vivo KD and OE Redox biology Medium 35779442
2022 A novel PRDX3 missense mutation (p.D163E) impairs the mitochondrial ROS defense system; the mutant protein is unstable, forms aggregates, triggers unfolded protein responses via both mitochondria and ER, and causes severe mitochondrial morphological alterations (damaged membranes, cristae disorganization) and accumulation of lipid droplets. Whole-exome sequencing; expression in mouse primary cortical neurons and HeLa cells; correlative light electron microscopy; mitochondrial functional parameters; fibroblast PRDX3 expression analysis; biochemical stability assays Human molecular genetics Medium 35766882
2023 During ferroptosis, mitochondrial lipid peroxides trigger PRDX3 hyperoxidation (converting catalytic Cys thiol to sulfinic or sulfonic acid); hyperoxidized PRDX3 then translocates from mitochondria to plasma membranes, where it inhibits cystine uptake, thereby promoting ferroptosis. This identifies hyperoxidized PRDX3 as a specific ferroptosis marker and establishes its membrane translocation as a pro-ferroptotic mechanism. In vitro ferroptosis assays; detection of PRDX3 hyperoxidation (SO2/3-PRDX3); subcellular fractionation and membrane localization; cystine uptake assay; in vivo mouse models of alcoholic and nonalcoholic fatty liver disease; immunohistochemistry Molecular cell High 37863053
2024 TRIM39 (E3 ubiquitin ligase) directly interacts with PRDX3 and induces its ubiquitination-mediated proteasomal degradation via K48-linked ubiquitin chains at lysine residues K73 and K149, leading to ROS accumulation and increased inflammatory cytokine generation that aggravates renal fibrosis. Co-immunoprecipitation (direct interaction); ubiquitination site mapping (K73, K149); K48 chain linkage determination; TRIM39 knockdown in UUO mouse model and HK-2 cells; ROS and inflammatory cytokine assays Cell death discovery Medium 38195664
2024 PRDX3 interacts with PINK1 to stabilize Parkin-mediated mitophagic flux; PRDX3 knockdown decreases PINK1 expression, accelerates mitochondrial quality control damage, and weakens the protective effect of SGLT2 inhibitor empagliflozin against diabetic nephropathy. PRDX3 overexpression (pcDNA3.1-PRDX3) and knockdown (siPrdx3); measurement of mitochondrial dynamics proteins (Mfn2, Drp1) and mitophagy proteins (PINK1, Parkin, LC3II, P62); in vivo diabetic mouse model Biochemical pharmacology Medium 39983849
2024 Human mitochondrial PRDX3 is dually localized to both the matrix and the intermembrane space (IMS) as soluble proteins; during import into the matrix, PRDX3 undergoes sequential proteolytic processing by mitochondrial processing peptidase (MPP) and mitochondrial intermediate peptidase (MIP); sorting to the IMS is dependent on the inner membrane peptidase (IMP) complex. Subfractionation of highly purified mitochondria from HEK293T cells with compartment markers; alkaline carbonate extraction; in organello import assays; heterologous expression in yeast; in silico analysis Redox biology High 39591905
2024 PRDX3 interacts with PINK1 in NPC cells (confirmed by co-immunoprecipitation and immunofluorescence); PRDX3 safeguards against apoptosis by sustaining PINK1/Parkin-dependent mitophagy clearance of damaged mitochondria, and PRDX3 knockdown suppresses NPC tumor growth in vivo. Co-immunoprecipitation; immunofluorescence co-localization; siRNA-mediated PRDX3 knockdown; mitophagy and apoptosis assays; xenograft tumor model Experimental cell research Medium 40912394
2025 KAT2A (succinyltransferase) interacts with PRDX3 and succinylates it at lysine K84; KAT2A knockdown inhibits PRDX3 succinylation at K84, enhances PRDX3 stability, and promotes M2 microglial polarization over M1. K84 mutation enhances the effect of wild-type PRDX3 on polarization. Co-immunoprecipitation; immunoprecipitation for succinylation; K84 site mutagenesis; KAT2A knockdown in BV2 cells and TBI mouse model; M1/M2 polarization marker quantification Neurological research Medium 40457625
2025 SIRT4 directly interacts with PRDX3 and deacetylates it at lysine K92; this deacetylation is required for SIRT4-mediated inhibition of ferroptosis in liver ischemia-reperfusion injury. Liver-specific SIRT4 overexpression is protective, while SIRT4 KO exacerbates liver injury and ferroptosis in a PRDX3-K92-deacetylation-dependent manner. Co-immunoprecipitation (SIRT4-PRDX3 interaction); site-specific K92 deacetylation mapping; SIRT4 KO and liver-specific OE mice; ferroptosis assays; ferrostatin-1 rescue; liver-targeted LNP-sirt4 mRNA delivery International journal of biological sciences Medium 40765819
2025 PRDX5 and PRDX3 cooperate in mitochondrial antioxidant defense during myogenesis: Prdx3-/-; Prdx5-/- double-knockout mice show accelerated muscle aging with increased mitochondrial H2O2 production, decreased muscle mass/strength, and elevated E3 ligases Atrogin1 and MuRF1 as early as 10 weeks; Prdx3 single KO reduces mitochondrial ATP production in myotubes. Prdx3-/-, Prdx5-/-, and double-KO mouse models; Seahorse OCR (mitochondrial ATP production); grip strength and treadmill performance; Atrogin1/MuRF1 expression; confocal/super-resolution microscopy of mitochondria Journal of cachexia, sarcopenia and muscle Medium 41147088
2026 PPT1 (palmitoyl-protein thioesterase 1) is the depalmitoylase of PRDX3: PPT1 catalyzes depalmitoylation of PRDX3 at its catalytic cysteine C108, thereby sustaining PRDX3 antioxidant activity. Genetic or chemical inhibition of PPT1 increases PRDX3 S-palmitoylation, elevates mitochondrial ROS, and induces cytotoxicity in multiple myeloma cells. Co-immunoprecipitation; S-palmitoylation assay; site-specific C108 identification; genetic and chemical PPT1 inhibition; mtROS measurement; xenograft tumor model Cellular signalling Medium 41865945
2025 ERβ (estrogen receptor β), stabilized by USP7-mediated deubiquitination, suppresses PRDX3 SUMOylation in NSCLC cells, thereby mitigating ROS accumulation and promoting osimertinib resistance; depletion of ERβ restores PRDX3 SUMOylation and reverses resistance. ERβ/USP7 Co-IP; PRDX3 SUMOylation assay; ERβ depletion in vitro and in vivo; ROS measurement; drug resistance (IC50) assays Cancer letters Medium 38097136

Source papers

Stage 0 corpus · 78 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 SIRT3-mediated deacetylation of PRDX3 alleviates mitochondrial oxidative damage and apoptosis induced by intestinal ischemia/reperfusion injury. Redox biology 194 31655428
2002 The c-Myc target gene PRDX3 is required for mitochondrial homeostasis and neoplastic transformation. Proceedings of the National Academy of Sciences of the United States of America 158 12011429
2023 Identification of hyperoxidized PRDX3 as a ferroptosis marker reveals ferroptotic damage in chronic liver diseases. Molecular cell 131 37863053
2007 Increased susceptibility of MER5 (peroxiredoxin III) knockout mice to LPS-induced oxidative stress. Biochemical and biophysical research communications 128 17316558
1997 SP-22 is a thioredoxin-dependent peroxide reductase in mitochondria. European journal of biochemistry 125 9363753
1999 Antioxidant function of the mitochondrial protein SP-22 in the cardiovascular system. The Journal of biological chemistry 114 9890990
1989 Cloning of a housekeeping-type gene (MER5) preferentially expressed in murine erythroleukemia cells. Gene 110 2583515
2010 Differential expression of peroxiredoxins in prostate cancer: consistent upregulation of PRDX3 and PRDX4. The Prostate 79 21031435
2022 The m6A reader YTHDF3-mediated PRDX3 translation alleviates liver fibrosis. Redox biology 74 35779442
2013 MiR-383 is downregulated in medulloblastoma and targets peroxiredoxin 3 (PRDX3). Brain pathology (Zurich, Switzerland) 68 23227829
1995 Possible function of SP-22, a substrate of mitochondrial ATP-dependent protease, as a radical scavenger. Biochemical and biophysical research communications 58 7654218
2003 Enhancement of mitochondrial oxidative stress and up-regulation of antioxidant protein peroxiredoxin III/SP-22 in the mitochondria of human pre-eclamptic placentae. Placenta 56 12828928
1998 Human T cell cyclophilin18 binds to thiol-specific antioxidant protein Aop1 and stimulates its activity. Journal of molecular biology 52 9545370
1994 Cloning and characterization of OSF-3, a new member of the MER5 family, expressed in mouse osteoblastic cells. Journal of biochemistry 45 8089076
1990 Antisense RNA of the latent period gene (MER5) inhibits the differentiation of murine erythroleukemia cells. Gene 45 2210385
1997 Copurification of vimentin, energy metabolism enzymes, and a MER5 homolog with nucleoside diphosphate kinase. Identification of tissue-specific interactions. The Journal of biological chemistry 44 9169432
2003 Structure-function analysis of recombinant substrate protein 22 kDa (SP-22). A mitochondrial 2-CYS peroxiredoxin organized as a decameric toroid. The Journal of biological chemistry 42 12773537
2020 High glucose-induced PRDX3 acetylation contributes to glucotoxicity in pancreatic β-cells: Prevention by Teneligliptin. Free radical biology & medicine 39 32763411
2012 Single nucleotide polymorphisms in the PRDX3 and RPS19 and risk of HPV persistence and cervical precancer/cancer. PloS one 38 22496757
2020 A novel circRNA, circNUP98, a potential biomarker, acted as an oncogene via the miR-567/ PRDX3 axis in renal cell carcinoma. Journal of cellular and molecular medicine 34 32729669
2021 Biallelic loss-of-function variations in PRDX3 cause cerebellar ataxia. Brain : a journal of neurology 32 33889951
2023 USP7-mediated ERβ stabilization mitigates ROS accumulation and promotes osimertinib resistance by suppressing PRDX3 SUMOylation in non-small cell lung carcinoma. Cancer letters 28 38097136
2016 Silencing PRDX3 Inhibits Growth and Promotes Invasion and Extracellular Matrix Degradation in Hepatocellular Carcinoma Cells. Journal of proteome research 28 26983019
2024 YAP1 inhibits the senescence of alveolar epithelial cells by targeting Prdx3 to alleviate pulmonary fibrosis. Experimental & molecular medicine 26 38945958
2013 siRNA targeting of PRDX3 enhances cisplatin‑induced apoptosis in ovarian cancer cells through the suppression of the NF‑κB signaling pathway. Molecular medicine reports 25 23503975
2021 Carnosol alleviates nonalcoholic fatty liver disease by inhibiting mitochondrial dysfunction and apoptosis through targeting of PRDX3. Toxicology and applied pharmacology 24 34678374
2016 Hydrogen peroxide mediated mitochondrial UNG1-PRDX3 interaction and UNG1 degradation. Free radical biology & medicine 21 27480846
2021 lnc-NLC1-C inhibits migration, invasion and autophagy of glioma cells by targeting miR-383 and regulating PRDX-3 expression. Oncology letters 18 34386062
2020 AOP1, a New Live Cell Assay for the Direct and Quantitative Measure of Intracellular Antioxidant Effects. Antioxidants (Basel, Switzerland) 18 32492957
2010 The combination of genetic variations in the PRDX3 gene and dietary fat intake contribute to obesity risk. Obesity (Silver Spring, Md.) 18 21127481
2014 Heart mitochondrial proteome study elucidates changes in cardiac energy metabolism and antioxidant PRDX3 in human dilated cardiomyopathy. PloS one 17 25397948
2007 Localization and H2O2-specific induction of PRDX3 in the eye lens. Molecular vision 16 17893648
2007 AOP-1 interacts with cardiac-specific protein kinase TNNI3K and down-regulates its kinase activity. Biochemistry. Biokhimiia 15 18205602
2024 FXN targeting induces cell death in ovarian cancer stem-like cells through PRDX3-Mediated oxidative stress. iScience 14 39184439
2022 Protein misfolding and clearance in the pathogenesis of a new infantile onset ataxia caused by mutations in PRDX3. Human molecular genetics 14 35766882
2021 Hsa_circ_0032131 knockdown inhibits osteoarthritis progression via the miR-502-5p/PRDX3 axis. Aging 14 34032607
2024 The E3 ubiquitin ligase TRIM39 modulates renal fibrosis induced by unilateral ureteral obstruction through regulating proteasomal degradation of PRDX3. Cell death discovery 13 38195664
2024 Activation of the FOXM1/ASF1B/PRDX3 axis confers hyperproliferative and antioxidative stress reactivity to gastric cancer. Cancer letters 12 38537775
2016 Plekhs1 and Prdx3 are candidate genes responsible for mild hyperglycemia associated with obesity in a new animal model of F344-fa-nidd6 rat. The Journal of veterinary medical science 11 27523322
2024 Human mitochondrial peroxiredoxin Prdx3 is dually localized in the intermembrane space and matrix subcompartments. Redox biology 10 39591905
2012 Identification of proteins containing redox-sensitive thiols after PRDX1, PRDX3 and GCLC silencing and/or glucose oxidase treatment in Hepa 1-6 cells. Journal of proteomics 10 22975676
2000 Expression of mitochondrial thioredoxin-dependent antioxidant protein, SP-22, in normal human and inflammatory mouse placentae. Placenta 10 11095935
1996 The cDNA sequence encoding bovine SP-22, a new defence system against reactive oxygen species in mitochondria. DNA sequence : the journal of DNA sequencing and mapping 10 8912927
2025 Empagliflozin attenuates renal damage in diabetic nephropathy by modulating mitochondrial quality control via Prdx3-PINK1 pathway. Biochemical pharmacology 9 39983849
2025 Histone lactylation protects against sevoflurane-induced cognitive impairment by regulating YTHDF3/PRDX3 mediated microglial pyroptosis in neonatal mice. International immunopharmacology 9 40022822
2022 PRDX3 promotes resistance to cisplatin in gastric cancer cells. Journal of cancer research and therapeutics 9 36647961
2023 Knockdown of circSOD2 ameliorates osteoarthritis progression via the miR-224-5p/PRDX3 axis. Journal of orthopaedic surgery and research 8 37312219
2012 [MicroRNA383 regulates expression of PRDX3 in human medulloblastomas]. Zhonghua bing li xue za zhi = Chinese journal of pathology 8 23157748
2022 Silencing of B7-H4 induces intracellular oxidative stress and inhibits cell viability of breast cancer cells via downregulating PRDX3. Neoplasma 7 35723197
2022 A novel biallelic variant further delineates PRDX3-related autosomal recessive cerebellar ataxia. Neurogenetics 7 36190665
2012 Involvement of Prx3, a Drosophila ortholog of the thiol-dependent peroxidase PRDX3, in age-dependent oxidative stress resistance. Biomedical research (Tokyo, Japan) 6 23124252
2025 SIRT4-Mediated Deacetylation of PRDX3 Attenuates Liver Ischemia Reperfusion Injury by Suppressing Ferroptosis. International journal of biological sciences 5 40765819
2024 Antioxidant PRDX3 gene therapy protects brain cells and prevents neurodegeneration in an animal model of Parkinson's disease. Neuropeptides 5 39736192
2022 A quantitative proteomic analysis reveals the potential roles of PRDX3 in neurite outgrowth in N2a-APPswe cells. Biochemical and biophysical research communications 5 35303681
2011 Immunohistochemical detection of metalloproteinase-9 (MMP-9), anti-oxidant like 1 protein (AOP-1) and synaptosomal-associated protein (SNAP-25) in the cerebella of dogs naturally infected with spontaneous canine distemper. Folia histochemica et cytobiologica 5 21526488
2025 The miR-320a/PRDX3 Axis Alleviates the Oxidative Stress and Fibrotic Alterations in Fibroblasts in Thyroid Eye Disease. Investigative ophthalmology & visual science 4 40657967
2024 Dexmedetomidine alleviates Hypoxia/reoxygenation-induced mitochondrial dysfunction in cardiomyocytes via activation of Sirt3/Prdx3 pathway. Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences 4 38407745
2023 Hyperoxidized PRDX3 as a specific ferroptosis marker. Life metabolism 4 38179338
2025 The pathogenesis of benign prostatic hyperplasia and the roles of Prdx3, oxidative stress, pyroptosis and autophagy:a review. Frontiers in oncology 3 40837016
2021 Confirmation of PRDX3 c.568G>C as the Genetic Basis of Punctiform and Polychromatic Pre-Descemet Corneal Dystrophy. Cornea 3 34369396
2025 Lycorine ameliorates astrocytic apoptosis and inflammation in cerebral ischemia/reperfusion injury via inhibiting mitochondrial dysfunction via SIRT1-mediated SIRT3/PRDX3 activation. Pathology, research and practice 2 40975001
2025 PRDX5 Regulates Mitochondrial Function and Nuclear Spreading in Myogenesis and Acts With PRDX3 to Delay Muscle Aging. Journal of cachexia, sarcopenia and muscle 2 41147088
2024 Ablation of Shank1 Protects against 6-OHDA-induced Cytotoxicity via PRDX3-mediated Inhibition of ER Stress in SN4741 Cells. CNS & neurological disorders drug targets 2 36797610
2014 Comparative study of Hsp27, GSK3β, Wnt1 and PRDX3 in Hirschsprung's disease. International journal of experimental pathology 2 24773279
2000 [Cell division in the volume of Flavobacterium sp.22 colonies]. Mikrobiologiia 2 10776626
2025 KAT2A knockdown induces microglia M2 polarization by succinylation of PRDX3 after traumatic brain injury. Neurological research 1 40457625
2025 Methylation of PRDX3 Expression Alleviate Ferroptosis and Oxidative Stress in Patients with Osteoarthritis Cartilage Injury. Archives of rheumatology 1 40757971
2025 PRDX3 promotes nasopharyngeal carcinoma tumor growth by regulating PINK1/Parkin pathway-dependent lipid peroxidation and mitochondrial dysfunction. Experimental cell research 1 40912394
2025 Atractylodin inhibits ferroptosis in sepsis‑induced acute gastrointestinal injury via SIRT3/PRDX3. Molecular medicine reports 1 40999974
2025 PRDX3 Promotes Lymph Node Metastasis in Cervical Cancer by Activating NF-κB Signaling Pathway and Anoikis Resistance. International journal of medical sciences 1 41049446
2025 Trace component fishing strategy based on offline two-dimensional liquid chromatography combined with PRDX3-surface plasmon resonance for Uncaria alkaloids. Journal of pharmaceutical analysis 1 41050113
2019 Chicken PRDX3 is required for proliferation of chicken embryo fibroblast cells. British poultry science 1 31615265
2026 Membrane-translocated SO₂/₃-PRDX3 disrupts cystine uptake and GPX4 activity: A pivotal mechanism of boron-induced renal ferroptosis in broiler. Ecotoxicology and environmental safety 0 41775182
2026 PPT1 regulates mitochondrial redox by depalmitoylating PRDX3. Cellular signalling 0 41865945
2026 Detecting ferroptotic cells using an antibody against hyperoxidized PRDX3. Methods in cell biology 0 42062006
2026 The integrated analysis of PRDX3 in lung cancer: biomarker potential and therapeutic target prospects. Respiratory research 0 42092925
2025 A homozygous PRDX3 pathogenic variant in a paediatric case of spinocerebellar ataxia type 32. Neurogenetics 0 41351775
2019 Molecular cloning, expression, purification, and functional characterization of SP-22 gene from Bombyx mori. Journal of cellular biochemistry 0 31099441

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