Affinage

CHCHD2

Coiled-coil-helix-coiled-coil-helix domain-containing protein 2 · UniProt Q9Y6H1

Length
151 aa
Mass
15.5 kDa
Annotated
2026-06-09
100 papers in source corpus 32 papers cited in narrative 33 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

CHCHD2 (MNRR1) is a bi-organellar regulator of mitochondrial bioenergetics and stress signaling that functions both as an intermembrane-space respiratory effector and as a nuclear transcription factor (PMID:25315652). Imported into the IMS via the Mia40 pathway through cysteines of its C-terminal CHCH domain, it binds directly to cytochrome c oxidase (Complex IV) and is required for full COX activity, membrane potential, and respiration (PMID:25315652, PMID:32068847); binding near helix IX of COX induces structural changes around the heme sites that accelerate proton uptake (PMID:39094247), and Abl2/ARG-mediated phosphorylation at Tyr-99 promotes its COX association and stimulates respiration (PMID:27913209). CHCHD2 partners with CHCHD10 in a high-molecular-weight heterodimeric complex required for efficient respiration and Complex I assembly, the two proteins being partially redundant in vivo (PMID:29121267, PMID:30084972, PMID:41053020). CHCHD2 maintains cristae architecture through interaction with the MICOS component Mic10 and, together with CHCHD10, restrains the stress peptidase OMA1 to prevent L-OPA1 cleavage and aberrant cristae remodeling (PMID:32338760, PMID:35173147, PMID:35830185); in Drosophila it stabilizes Opa1 by displacing P32 from the YME1L protease (PMID:31907391). It suppresses apoptosis by binding Bcl-xL to block Bax oligomerization and MOMP, and modulates cell death together with cytochrome c and MICS1 (PMID:25476776, PMID:28589937). In the nucleus, CHCHD2 binds an oxygen-responsive element (ORE) with RBPJκ and the co-activator p300 to activate hypoxia-responsive and mitochondrial-recovery genes including COX4I2, and drives the mitochondrial unfolded protein response upstream of ATF5 (PMID:25315652, PMID:33257573, PMID:41592630). The Parkinson's-disease-linked T61I mutation precipitates within the IMS with dominant-negative effects on wild-type CHCHD2, mislocalizes to the cytosol where it recruits casein kinase 1ε/δ to phosphorylate α-synuclein, and impairs F1F0-ATPase assembly (PMID:32068847, PMID:37578019, PMID:37488867); CHCHD2 deficiency lowers α-ketoglutarate dehydrogenase, driving lipid peroxidation and α-synuclein aggregation, establishing a direct mechanistic link to neurodegeneration (PMID:40011434, PMID:41237231).

Mechanistic history

Synthesis pass · year-by-year structured walk · 30 steps
  1. 2014 High

    Established CHCHD2 as a dual-function protein: an IMS effector required for Complex IV activity and a hypoxia-responsive nuclear transcription factor, defining its bi-organellar nature.

    Evidence Subcellular fractionation, Co-IP with COX, respiration assays, promoter-reporter and ChIP under normoxia vs. hypoxia

    PMID:25315652

    Open questions at the time
    • Molecular signal switching import vs. nuclear retention not fully resolved
    • Direct DNA-binding mode at the ORE not structurally defined
  2. 2014 High

    Showed CHCHD2 acts as an anti-apoptotic guardian at mitochondria, answering how it couples bioenergetics to cell-death control.

    Evidence Reciprocal Co-IP with Bcl-xL, Bax oligomerization, cytochrome c release and MOMP assays

    PMID:25476776

    Open questions at the time
    • Whether Bcl-xL binding is direct or bridged not resolved
    • Quantitative contribution to apoptosis in vivo unclear
  3. 2015 Medium

    Linked CHCHD2 to a broader interactome (C1QBP, YBX1) and a pro-migratory role in cancer cells, extending function beyond classical mitochondrial biology.

    Evidence AP-MS and proximity ligation interactome mapping with knockdown migration/respiration assays in NSCLC

    PMID:25784717

    Open questions at the time
    • Direct vs. indirect nature of YBX1 interaction unproven
    • Mechanism connecting respiration to migration not defined
  4. 2016 High

    Identified the post-translational control of COX binding through Abl2/ARG phosphorylation at Tyr-99, mechanizing how respiration is tuned and how a disease mutation impairs it.

    Evidence Site-directed mutagenesis, in vitro kinase assay, Co-IP with Abl2 and COX, oxygen consumption

    PMID:27913209

    Open questions at the time
    • Phosphatase that reverses Y99 not identified
    • Stoichiometry of phospho-CHCHD2 in vivo unknown
  5. 2016 Medium

    Revealed a non-respiratory developmental role: CHCHD2 sequesters SMAD4 at mitochondria to suppress TGFβ signaling and prime neuroectodermal differentiation.

    Evidence Co-IP, fractionation, TGFβ reporter assay, differentiation readout in pluripotent stem cells

    PMID:27810911

    Open questions at the time
    • Single lab without reciprocal in vivo validation
    • How mitochondrial sequestration is regulated unclear
  6. 2017 High

    Confirmed cytochrome c/MICS1 partnership and demonstrated, in an in vivo dopaminergic model, that PD mutants fail to rescue CHCHD2 loss, tying the gene to neurodegeneration.

    Evidence Co-IP, Drosophila KO/rescue with WT vs. mutant human CHCHD2, EM, neuron counting

    PMID:28589937

    Open questions at the time
    • Mammalian relevance of MICS1 interaction not directly shown
    • Mechanism of mutant loss-of-function not dissected here
  7. 2018 High

    Defined the CHCHD2–CHCHD10 heterodimeric complex as the functional respiratory unit and showed ALS-linked CHCHD10 variants destabilize it, unifying two disease genes mechanistically.

    Evidence Reciprocal Co-IP, BN-PAGE, respiration assays in patient fibroblasts, KO cell lines, IF co-localization

    PMID:29121267 PMID:30084972

    Open questions at the time
    • Stoichiometry and structure of the ~220 kDa complex undefined
    • How the complex is distributed across cristae not mechanized
  8. 2018 Medium

    Showed CHCHD10 scaffolds CHCHD2 phosphorylation by ARG and that nuclear CHCHD10 opposes CHCHD2 at ORE genes via CXXC5, revealing reciprocal regulation.

    Evidence Co-purification with COX, Co-IP of CHCHD10/CHCHD2/ARG, COX activity and gene expression assays

    PMID:29540477

    Open questions at the time
    • Direct vs. indirect scaffolding of the kinase unresolved
    • Generality of CXXC5 repression across ORE genes unknown
  9. 2019 High

    Connected PD-associated CHCHD2 mutations to MICOS disruption and cristae collapse, mechanizing the structural consequence of disease alleles.

    Evidence Isogenic CRISPR hESC lines, STED super-resolution, Co-IP, EM of cristae

    PMID:30496485

    Open questions at the time
    • Direct MICOS subunit contacts not mapped
    • Whether cristae loss is cause or consequence of respiratory defect unclear
  10. 2020 High

    Established that CHCHD2/CHCHD10 loss activates OMA1 to cleave L-OPA1, identifying the protease axis that links the complex to cristae and fusion control.

    Evidence DKO and mutant CHCHD10 knock-in mice, OMA1 activity and OPA1 cleavage immunoblots, EM

    PMID:32338760

    Open questions at the time
    • Direct OMA1 binding shown later; activation mechanism not fully defined here
    • Tissue specificity of redundancy not characterized
  11. 2020 High

    Identified the YME1L/P32 competition mechanism by which CHCHD2 stabilizes OPA1 and controls mitochondrial morphology.

    Evidence Drosophila KO, Co-IP with P32 and YME1L, protease activity assay, genetic epistasis

    PMID:31907391

    Open questions at the time
    • Conservation of the P32/YME1L mechanism in mammals not confirmed here
    • Quantitative balance between YME1L and OMA1 axes unclear
  12. 2020 High

    Defined the molecular pathology of the T61I mutation: IMS precipitation with dominant-negative aggregation of wild-type protein, and mapped CHCH-domain cysteines as the true mitochondrial targeting determinant.

    Evidence Fractionation, detergent solubility assays, cysteine mutagenesis, live-cell imaging, ROS/apoptosis assays

    PMID:32068847

    Open questions at the time
    • Structural basis of aggregation not determined
    • Why T61I specifically destabilizes the fold not resolved
  13. 2020 High

    Showed CHCHD2's nuclear transcription function drives UPRmt, autophagy, and biogenesis to rescue mitochondrial disease, placing it upstream of ATF5.

    Evidence Overexpression in MELAS cybrids, UPRmt/autophagy/biogenesis markers, ATF5 quantification in KO cells

    PMID:33257573

    Open questions at the time
    • Whether CHCHD2 directly transactivates ATF5 not shown
    • Relative contribution of nuclear vs. mitochondrial pools to rescue unclear
  14. 2022 Medium

    Demonstrated direct OMA1 binding and stress-induced cytosolic translocation where CHCHD2/CHCHD10 engage eIF2α to restrain mtISR over-activation.

    Evidence Co-IP with OMA1 and eIF2α, OMA1 activity assay, eIF2α phosphorylation, fractionation after CCCP

    PMID:35173147

    Open questions at the time
    • Direct vs. indirect eIF2α interaction not fully established
    • Single lab without reciprocal validation
  15. 2022 Medium

    Identified Mic10 as a CHCHD2 MICOS partner and showed CHCHD2 overexpression protects against toxin-induced MICOS impairment and neuron loss.

    Evidence Co-IP with Mic10, BN-PAGE/2D-SDS-PAGE for MICOS stability, AAV overexpression in MPTP mice

    PMID:35830185

    Open questions at the time
    • Direct binding interface with Mic10 not mapped
    • Single lab
  16. 2022 Medium

    Showed in zebrafish that single CHCHD2 loss impairs Complex I and neuromuscular function but double KO restores Complex I via mt-ISR, revealing a compensatory stress response.

    Evidence CRISPR single and double KO zebrafish, BN-PAGE Complex I assembly, motor and NMJ assays

    PMID:36799027

    Open questions at the time
    • Mechanism of mt-ISR-mediated Complex I restoration not defined
    • Single model organism
  17. 2022 Medium

    Extended CHCHD2's nuclear role to liver disease, showing it drives fibrosis via Notch/osteopontin and is induced through YAP/TAZ-TEAD.

    Evidence ChIP-seq, hepatocyte-specific OE/KO mice, Notch inhibition rescue, verteporfin treatment

    PMID:36477358

    Open questions at the time
    • Direct target genes vs. indirect effects not fully separated
    • Connection to mitochondrial function in liver unclear
  18. 2023 High

    Mechanized the T61I gain-of-function in neurodegeneration: cytosolic mislocalization recruits CK1ε/δ to phosphorylate α-synuclein, and kinase inhibition rescues phenotypes.

    Evidence Co-IP with Csnk1e/d, phospho-α-synuclein and aggresome assays, T61I KI/transgenic mice, inhibitor rescue in mice and iPSC neurons

    PMID:37578019

    Open questions at the time
    • How mislocalized CHCHD2 recruits the kinase mechanistically unclear
    • Generality across other CHCHD2 mutants not tested
  19. 2023 Medium

    Revealed a genome-stability role: CHCHD2 represses RNase H1 transcription with Sirt1 as co-repressor, promoting R-loop accumulation.

    Evidence ChIP and Co-IP with Sirt1, gene expression after CHCHD2/G9a knockdown, R-loop quantification

    PMID:37388553

    Open questions at the time
    • Physiological context of R-loop regulation unclear
    • Single lab without orthogonal validation
  20. 2024 Medium

    Provided spectroscopic evidence for how CHCHD2 binding remodels COX heme architecture to accelerate proton uptake, mechanizing its respiratory activation.

    Evidence Visible resonance Raman spectroscopy of purified COX with and without CHCHD2

    PMID:39094247

    Open questions at the time
    • No mutagenesis validation of the proposed helix contacts
    • Single method, single lab
  21. 2024 High

    Defined a CHCHD2-specific metabolic axis: deficiency lowers KGDH, raising α-ketoglutarate and lipid peroxidation, with lipoic acid rescuing p-α-synuclein.

    Evidence Unbiased mitochondrial metabolomics, KGDH quantification in KO mouse brain and iPSC neurons, lipoic acid rescue, CHCHD10 KO control

    PMID:40011434

    Open questions at the time
    • How CHCHD2 loss lowers KGDH protein not mechanized
    • Link between α-KG elevation and lipid peroxidation not fully traced
  22. 2024 Medium

    Identified CHCHD2 regulation of F1F0-ATPase assembly and the T61I loss of this function in PD cell and mouse models.

    Evidence MS and Co-IP with F1F0-ATPase, BN-PAGE assembly, WT vs. T61I in MPP+ cells, MPTP/AAV mouse model

    PMID:37488867

    Open questions at the time
    • Direct binding interface with ATPase subunits unmapped
    • Single lab
  23. 2024 Medium

    Placed CHCHD2 in a C1QBP/CHCHD2/CHCHD10 ternary complex regulating protein stability and neural cell viability under stress.

    Evidence Co-IP of ternary complex, CHCHD2 deficiency models, mitochondrial function and autophagy assays

    PMID:38453793

    Open questions at the time
    • Architecture and stoichiometry of ternary complex unknown
    • Single lab
  24. 2024 Medium

    Showed CHCHD2 loss in pluripotent stem cells epigenetically attenuates ROCK activity, conferring dissociation resistance, broadening its regulatory reach.

    Evidence Transcriptome/methylome analysis, knockdown/reconstitution, ROCK activity and survival assays in hESCs

    PMID:38214772

    Open questions at the time
    • Mechanistic link between CHCHD2 and ROCK indirect
    • Single lab
  25. 2024 Medium

    Identified HIF2α as a repressor of the CHCHD2 promoter via RBPJκ competition, mechanizing pseudohypoxic CHCHD2 loss in MELAS.

    Evidence ChIP, HIF2α vs. RBPJκ promoter competition assay, PHD3 quantification in MELAS cybrids

    PMID:40710331

    Open questions at the time
    • Generality across cell types not established
    • Single lab
  26. 2025 Medium

    Demonstrated in MASH liver that ClpXP-mediated degradation controls CHCHD2 levels and that elevated CHCHD2 drives VEGFA-dependent angiogenesis supporting HCC.

    Evidence ChIP-seq, KO and hepatocyte-specific OE mice, ClpXP protease assay, orthotopic HCC model

    PMID:40025232

    Open questions at the time
    • Direct ClpXP recognition motif on CHCHD2 not defined
    • Mitochondrial vs. nuclear pool driving VEGFA unclear
  27. 2025 High

    Comprehensively characterized the T61I knock-in mouse, linking IMS aggregation, glycolytic metabolic shift, and α-synuclein pathology to human Lewy aggregate accumulation.

    Evidence CRISPR T61I KI mice, immuno-EM, spatial genomics, mitochondrial proteomics, metabolic phenotyping, human PD brain IF

    PMID:41237231

    Open questions at the time
    • Temporal sequence of metabolic shift vs. aggregation not resolved
    • Whether CHCHD2 accumulation initiates or follows Lewy pathology unclear
  28. 2026 Medium

    Mapped the nuclear transactivation mechanism to RBPJκ binding and p300 recruitment at the ORE, with a minimal peptide sufficient to activate transcription.

    Evidence Co-IP of CHCHD2/RBPJκ/p300, domain deletion, peptide activation assay, downstream UPRmt/biogenesis readouts in MELAS

    PMID:41592630

    Open questions at the time
    • Structural basis of CHCHD2-RBPJκ-p300 assembly undefined
    • Single lab
  29. 2026 Medium

    Revealed an autophagy-regulatory function: CHCHD2/CHCHD10 with C1QBP bind GABARAPs to recruit ULK1 and initiate autophagy, promoting α-synuclein clearance.

    Evidence Co-IP of CHCHD2-CHCHD10-C1QBP-ATG8 complex, ATG8 specificity, ULK1 recruitment, autophagy in KO iPSC neurons, α-synuclein assay

    PMID:42183628

    Open questions at the time
    • Whether autophagy role is mitochondria-localized or cytosolic unclear
    • Single lab
  30. 2026 Low

    Reported that CHCHD2 knockdown reduces mtUPR proteins via JNK/c-Jun and AKT/ERα pathways in a PD cell model.

    Evidence shRNA knockdown in MPP+-treated SH-SY5Y, Western blot, JNK/AKT agonist treatment, EM

    PMID:41640382

    Open questions at the time
    • Pharmacological agonists used without genetic epistasis confirmation
    • Single lab, single cell model

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the bi-organellar partition of CHCHD2 is dynamically controlled and how its mitochondrial structural/respiratory roles mechanistically converge with its nuclear transcriptional program to determine neuronal vulnerability remains unresolved.
  • No unified model linking respiratory, cristae, and transcriptional functions
  • Structure of the CHCHD2/CHCHD10 complex undefined
  • Causal hierarchy among bioenergetic, metabolic, and aggregation defects in disease unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0098772 molecular function regulator activity 5 GO:0003677 DNA binding 3 GO:0140313 molecular sequestering activity 1
Localization
GO:0005634 nucleus 4 GO:0005739 mitochondrion 4 GO:0005829 cytosol 3
Pathway
R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 1
Partners
BCL-XLC1QBPCHCHD10COX (CYTOCHROME C OXIDASE)MIC10OMA1RBPJYME1L
Complex memberships
C1QBP/CHCHD2/CHCHD10 ternary complexCHCHD2-CHCHD10 heterodimeric complexCytochrome c oxidase (Complex IV) associationMICOS

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 CHCHD2 (MNRR1) is imported to the mitochondrial intermembrane space (IMS) via a Mia40-mediated pathway, where it binds directly to cytochrome c oxidase (COX/Complex IV), and this association is required for full COX activity. Loss of CHCHD2 reduces COX activity, membrane potential, and growth rate while increasing ROS and mitochondrial fragmentation. Subcellular fractionation, co-immunoprecipitation with COX, functional respiration assays, knockdown with defined phenotypic readouts Mitochondrion High 25315652
2014 In the nucleus, CHCHD2 (MNRR1) functions as a transcription factor that binds a novel oxygen-responsive element (ORE) in the promoter of COX4I2 (and itself) to stimulate transcription under hypoxia (4% oxygen). During stress, import into mitochondria is blocked, causing nuclear accumulation and enhanced transcriptional activity. Promoter-reporter assays, chromatin immunoprecipitation (ChIP), subcellular fractionation under normoxic vs. hypoxic conditions, knockdown/overexpression Mitochondrion High 25315652
2014 CHCHD2 binds to Bcl-xL at the mitochondria and inhibits mitochondrial accumulation and oligomerization of Bax, thereby suppressing mitochondrial outer membrane permeabilization (MOMP) and apoptosis. CHCHD2 levels decrease prior to MOMP in response to apoptotic stimuli, and its absence attenuates Bcl-xL's ability to block Bax activation. Co-immunoprecipitation (CHCHD2/Bcl-xL), overexpression and knockdown with Bax oligomerization assay, cytochrome c release assay, MOMP assay Cell death and differentiation High 25476776
2016 Phosphorylation of CHCHD2 (MNRR1) at tyrosine-99 by Abl2 kinase (ARG) inside mitochondria promotes its binding to COX and stimulates respiration. A disease-associated Q112H mutation impairs interaction with Abl2, leading to defective tyrosine phosphorylation and reduced respiration. Site-directed mutagenesis (Y99 phosphorylation site), in vitro kinase assay, Co-IP of CHCHD2 with Abl2 and COX, oxygen consumption assay Biochimica et biophysica acta. Molecular cell research High 27913209
2017 CHCHD2 binds cytochrome c together with MICS1 (a Bax inhibitor-1 superfamily member) to modulate cell death signalling. Loss of CHCHD2 in Drosophila disrupts mitochondrial matrix/crista structures, impairs oxygen respiration, causes oxidative stress, and leads to dopaminergic neuron loss; these phenotypes are rescued by human CHCHD2 but not by PD-associated mutants. Co-immunoprecipitation (CHCHD2/cytochrome c/MICS1), Drosophila CHCHD2 knockout/overexpression, electron microscopy, oxygen consumption assay, dopaminergic neuron counting, genetic rescue with human WT vs. mutant CHCHD2 Nature communications High 28589937
2018 CHCHD2 and CHCHD10 form a high-molecular-weight (~220 kDa) heterodimeric complex required for efficient mitochondrial respiration. The ALS-linked CHCHD10 p.R15L variant destabilizes CHCHD10, abolishes this complex, and impairs Complex I assembly and cellular respiration. Reciprocal co-immunoprecipitation (CHCHD2/CHCHD10), blue-native PAGE, oxygen consumption assay in patient fibroblasts, galactose proliferation assay Human molecular genetics High 29121267
2018 CHCHD2 accumulates preferentially in distressed mitochondria (upon loss of membrane potential), while CHCHD10 oligomerization depends on CHCHD2 expression. CHCHD2 and CHCHD10 form heterodimers distributed throughout mitochondrial cristae; disease-causing mutations in either protein can still form heterodimers. CHCHD2/CHCHD10 double knockout cell lines, Blue-native PAGE, immunofluorescence co-localization, heterodimer incorporation assay, mitochondrial stress induction Human molecular genetics High 30084972
2018 CHCHD10 serves as a scaffolding protein required for CHCHD2 (MNRR1) phosphorylation by ARG/Abl2 kinase; CHCHD10 co-purifies with COX and up-regulates COX activity. In the nucleus, CHCHD10 down-regulates ORE-containing gene expression by interacting with and augmenting transcriptional repressor CXXC5. Co-purification with COX, Co-IP (CHCHD10/CHCHD2/ARG), COX activity assay, nuclear CHCHD10 interaction with CXXC5, gene expression analysis The Journal of biological chemistry Medium 29540477
2019 PD-associated CHCHD2 mutations R145Q and Q126X reduce interaction with CHCHD10 and disrupt the MICOS (mitochondrial contact site and cristae organizing system) complex, leading to hollow mitochondria with reduced cristae. Wild-type CHCHD2 physically colocalizes with MICOS components by super-resolution microscopy. CRISPR-Cas9 isogenic hESC lines, super-resolution microscopy (STED), co-immunoprecipitation (CHCHD2/CHCHD10), MICOS component quantification, electron microscopy of cristae Human molecular genetics High 30496485
2020 Loss of CHCHD2 and CHCHD10 activates the mitochondrial stress-induced peptidase OMA1, which cleaves L-OPA1, thereby disrupting mitochondrial cristae. CHCHD2/CHCHD10 are partially functionally redundant; mutant CHCHD10 knock-in mice show the same OMA1 activation and L-OPA1 cleavage phenotype. CHCHD2/CHCHD10 double-knockout mice, OMA1 activity assay, OPA1 cleavage assay by immunoblot, mutant CHCHD10 knock-in mice, electron microscopy Human molecular genetics High 32338760
2020 Drosophila Chchd2 regulates mitochondrial morphology by stabilizing Opa1 protein levels. Chchd2 competes with the chaperone-like protein P32 for binding to YME1L protease; P32-YME1L interaction enhances Opa1 degradation, and Chchd2 stabilizes Opa1 by displacing P32 from YME1L. Co-immunoprecipitation confirmed Chchd2 interaction with P32 and YME1L. Drosophila Chchd2 knockout, co-immunoprecipitation (Chchd2/P32/YME1L), YME1L activity assay, OPA1 protein level quantification, epistasis with Marf overexpression and Opa1 RNAi Cell death and differentiation High 31907391
2020 The T61I CHCHD2 mutation causes its precipitation (insolubility) inside the mitochondrial IMS, and T61I CHCHD2 exerts a dominant-negative effect by impairing the solubility of wild-type CHCHD2. Mitochondrial targeting of CHCHD2 depends on the four cysteine residues in the C-terminal CHCH domain, not on the N-terminal predicted targeting sequence. Subcellular fractionation, solubility assay (detergent-based), cysteine mutagenesis of CHCH domain, live-cell fluorescence microscopy, ROS and apoptosis assays Human molecular genetics High 32068847
2020 CHCHD2 (MNRR1) overexpression in MELAS cells induces the mitochondrial unfolded protein response (UPRmt), autophagy, and mitochondrial biogenesis, rescuing the mitochondrial phenotype. This rescue operates primarily through CHCHD2's nuclear transcription activator function. CHCHD2 acts upstream of the UPRmt mediator ATF5; CHCHD2 knockout cells display ~40% reduction in ATF5 protein. Overexpression in MELAS cybrid cells, UPRmt marker quantification, autophagy assay, ATF5 protein quantification in CHCHD2-KO cells, mitochondrial biogenesis assay Proceedings of the National Academy of Sciences of the United States of America High 33257573
2016 CHCHD2 primes neuroectodermal differentiation of pluripotent stem cells by binding and sequestering SMAD4 to the mitochondria, thereby suppressing TGFβ signaling pathway activity. Co-immunoprecipitation (CHCHD2/SMAD4), subcellular fractionation, SMAD4 localization by immunofluorescence, TGFβ reporter assay, CHCHD2 knockdown/overexpression with neuroectodermal differentiation readout The Journal of cell biology Medium 27810911
2022 CHCHD2 and CHCHD10 interact with OMA1 in physiological conditions and suppress its enzymatic activity, restraining both the initiation of mitochondrial integrated stress response (mtISR) and OPA1 processing for mitochondrial fusion. During mitochondrial stress (CCCP), CHCHD2 and CHCHD10 translocate to the cytosol and interact with eIF2α, attenuating mtISR over-activation by suppressing eIF2α phosphorylation. Co-immunoprecipitation (CHCHD2/CHCHD10 with OMA1 and eIF2α), OMA1 activity assay, eIF2α phosphorylation assay, subcellular fractionation after CCCP treatment, CHCHD2/CHCHD10 knockdown Cell death & disease Medium 35173147
2023 CHCHD2 T61I mutant protein mislocalizes to the cytosol in Neuro2a cells and recruits casein kinase 1ε/δ (Csnk1e/d), which then phosphorylates neurofilament and α-synuclein, forming cytosolic aggresomes. A Csnk1e/d inhibitor suppresses this phosphorylation and improves neurodegeneration phenotypes in Chchd2 T61I mice. Fluorescence microscopy (T61I mislocalization), co-immunoprecipitation (CHCHD2/Csnk1e/d), phospho-α-synuclein assay, aggresome quantification, in vivo T61I knock-in and transgenic mice, pharmacologic Csnk1e/d inhibitor rescue in mice and iPSC-derived neurons EMBO molecular medicine High 37578019
2024 CHCHD2 deficiency reduces α-ketoglutarate dehydrogenase (KGDH) complex protein levels in mouse brain and human dopaminergic neurons, leading to elevated α-ketoglutarate and increased lipid peroxidation. Treatment with lipoic acid (a KGDH cofactor/antioxidant) reduces lipid peroxidation and phosphorylated α-synuclein in CHCHD2-deficient neurons. This KGDH pathway effect is specific to CHCHD2 and not CHCHD10. Unbiased metabolomics of purified mitochondria, KGDH protein quantification in KO mouse brain and iPSC-derived dopaminergic neurons, lipoic acid treatment with lipid peroxidation and p-α-synuclein assay, CHCHD10 KO comparison Nature communications High 40011434
2024 CHCHD2 binds near helix IX of COX (exposed in the IMS) and induces structural changes around the heme sites, particularly around helix X (located between both hemes), thereby accelerating proton uptake in the reduced state for proton pumping. Visible resonance Raman spectroscopy of purified COX in reduced and CO-bound states with and without CHCHD2 binding Journal of inorganic biochemistry Medium 39094247
2024 CHCHD2 interacts with F1F0-ATPase (confirmed by mass spectrometry and co-immunoprecipitation), and wild-type CHCHD2 overexpression promotes F1F0-ATPase assembly. The T61I mutant has lost the ability to regulate F1F0-ATPase assembly, contributing to mitochondrial dysfunction in a PD cell model. Mass spectrometry, co-immunoprecipitation (CHCHD2/F1F0-ATPase), BN-PAGE for ATPase assembly, overexpression of WT vs. T61I in MPP+-treated SH-SY5Y cells, in vivo MPTP mouse model with AAV-T61I Neural regeneration research Medium 37488867
2022 CHCHD2 interacts with Mic10 (a MICOS component) as shown by co-immunoprecipitation; overexpression of CHCHD2 protects against MPP+-induced MICOS impairment, while CHCHD2 knockdown destabilizes MICOS. CHCHD2 overexpression protects against MPP+-induced mitochondrial dysfunction and inhibits dopaminergic neuron loss in an MPTP mouse model. Co-immunoprecipitation (CHCHD2/Mic10), BN-PAGE, 2D-SDS-PAGE for MICOS stability, AAV-mediated CHCHD2 overexpression in MPTP mice with dopaminergic neuron counting Chinese medical journal Medium 35830185
2024 C1QBP (a mitochondrial protein) regulates the stability of CHCHD2 and CHCHD10 proteins and maintains the integrity of a C1QBP/CHCHD2/CHCHD10 ternary complex. CHCHD2 deficiency leads to decreased neural cell viability and mitochondrial structural and functional impairment with upregulated autophagy under cellular stress. Co-immunoprecipitation (C1QBP/CHCHD2/CHCHD10 complex), CHCHD2 deficiency models (siRNA and in vivo), mitochondrial function assays, autophagy/mitophagy quantification, cell viability assay Molecular neurobiology Medium 38453793
2023 CHCHD2 acts as a repressive transcription factor at the RNase H1 promoter to inhibit RNase H1 expression and promote R-loop accumulation. Sirt1 deacetylates CHCHD2 and acts as a co-repressor, enhancing CHCHD2-mediated suppression of RNase H1 transcription. G9a methylase prevents CHCHD2/Sirt1 recruitment to the RNase H1 promoter. ChIP assay (CHCHD2/Sirt1 at RNase H1 promoter), co-immunoprecipitation (CHCHD2/Sirt1), gene expression assays after CHCHD2 knockdown/G9a knockdown, R-loop quantification Cell insight Medium 37388553
2024 HIF2α binds the CHCHD2 (MNRR1) promoter and inhibits transcription by competing with the transcriptional activator RBPJκ. In MELAS cells a pseudohypoxic state stabilizes HIF2α (via reduced PHD3), thereby reducing CHCHD2 levels. ChIP assay (HIF2α at MNRR1 promoter), promoter competition assay (HIF2α vs. RBPJκ), PHD3 quantification in MELAS cybrids, HIF2α knockdown/stabilization experiments Cells Medium 40710331
2026 CHCHD2 transcriptional activation requires interaction with RBPJκ and recruitment of the co-activator p300 to the ORE promoter element. A minimal domain of CHCHD2 is sufficient for nuclear function, and peptides based on this domain can activate transcription by enhancing p300-RBPJκ interaction. Co-immunoprecipitation (CHCHD2/RBPJκ/p300), domain deletion analysis, peptide-based activation assay, downstream pathway (UPRmt, biogenesis) activation in MELAS model Mitochondrion Medium 41592630
2026 CHCHD2 and CHCHD10 form a complex with C1QBP/p32 and ATG8-family proteins (preferentially GABARAPs). Through GABARAP binding, CHCHD2/CHCHD10 undergo autophagic degradation and recruit the ULK1 complex to activate autophagy initiation. CHCHD2 promotes clearance of toxic α-synuclein species and reduces protein aggregates. Co-immunoprecipitation of CHCHD2-CHCHD10-C1QBP-ATG8 complex, ATG8 binding specificity assay (GABARAPs vs. LC3s), ULK1 complex recruitment assay, autophagy initiation assay in CHCHD2 KO iPSC-derived neurons, α-synuclein aggregate quantification in mouse striatum Autophagy Medium 42183628
2024 Loss of CHCHD2 epigenetically (by promoter methylation) attenuates Rho-associated protein kinase (ROCK) activity in human pluripotent stem cells, conferring resistance to single-cell dissociation-induced death during in vitro culture. Transcriptome and methylome analysis, CHCHD2 knockdown and reconstitution in hESCs, ROCK activity assay, cell survival assay under enzymatic dissociation Cellular and molecular life sciences Medium 38214772
2025 CHCHD2 T61I knock-in mice show pronounced mitochondrial disruption (distorted ultrastructure and CHCHD2 aggregation) in substantia nigra dopaminergic neurons, disrupted mitochondrial protein-protein interactions, a whole-body metabolic shift toward glycolysis, elevated mitochondrial ROS, and progressive α-synuclein aggregation. In idiopathic PD, CHCHD2 protein accumulates in early Lewy aggregates, linking CHCHD2 accumulation to α-synuclein pathology. CRISPR knock-in T61I mice, immune-electron microscopy, spatial genomics, proteomics (mitochondrial PPI), metabolic phenotyping (RER), α-synuclein aggregation assay, human PD brain immunofluorescence Science advances High 41237231
2022 Loss of CHCHD2 in zebrafish impairs Complex I assembly and causes motor impairment, reduced survival, and compromised neuromuscular junction integrity. However, in chchd2/chchd10 double KO zebrafish, Complex I is paradoxically restored and the mt-ISR is activated, suggesting that mt-ISR activation can compensate for the Complex I defect seen in single KOs. Zebrafish CRISPR knockout (chchd2-/-, chchd10-/-, double KO), Complex I assembly assay (BN-PAGE), behavioral motor assay, neuromuscular junction staining, mt-ISR transcriptional marker assay Developmental neurobiology Medium 36799027
2022 CHCHD2 and CHCHD10 exist exclusively as a high-molecular-weight complex in mouse tissues in vivo; this complex increases in abundance and size in response to mitochondrial dysfunction across different tissues. Loss of CHCHD2 does not abolish CHCHD10 oligomerization but enhances cell vulnerability to mitochondrial stress. CHCHD2 KO mice display impaired motor capacity, reduced striatal dopamine levels, and lipid homeostasis disruption in the brain. Whole-body Chchd2 KO mice, BN-PAGE, mitochondrial stress induction, motor behavior assay, dopamine quantification, lipidomics Cell death & disease Medium 41053020
2026 CHCHD2 knockdown markedly reduces expression of mtUPR-related proteins (HSPA9, HSPD1, YME1L1, CLPP) in an MPP+-induced PD cell model, and the mtUPR activation by CHCHD2 involves the JNK/c-Jun and AKT/ERα pathways. shRNA knockdown of CHCHD2 in MPP+-treated SH-SY5Y cells, Western blot for mtUPR proteins, JNK and AKT agonist treatment, electron microscopy of mitochondrial morphology ACS chemical neuroscience Low 41640382
2015 CHCHD2 promotes cell migration and regulates mitochondrial respiration in NSCLC cells. Protein-protein interaction mapping identified C1QBP (mitochondrial hub) and YBX1 (oncogenic transcription factor) as CHCHD2 interactors by affinity purification mass spectrometry and proximity ligation. CHCHD2 knockdown in NSCLC cells (migration assay, proliferation assay, oxygen consumption), affinity purification mass spectrometry, proximity ligation assay Molecular cancer research Medium 25784717
2022 CHCHD2 acts as a nuclear transcription factor in NASH liver; ChIP-seq identified CHCHD2 target genes enriched in NAFLD pathways. CHCHD2 promotes liver fibrosis via Notch signaling by up-regulating osteopontin in hepatocytes, which activates hepatic stellate cells. LPS-induced CHCHD2 expression in hepatocytes is dependent on YAP/TAZ-TEAD. ChIP sequencing (CHCHD2 target genes), hepatocyte-specific CHCHD2 overexpression/knockout mice, Notch inhibition rescue, osteopontin quantification, YAP/TAZ inhibitor (verteporfin) treatment JCI insight Medium 36477358
2025 In MASH liver, CHCHD2 protein degradation is primarily mediated by the mitochondrial protease ClpXP, which is repressed in MASH. Elevated CHCHD2 promotes VEGFA transcription (identified by ChIP-seq) in hepatocytes, leading to increased angiogenic activity and supporting HCC growth. CHCHD2 ChIP-seq, Chchd2 KO mice, AAV-mediated hepatocyte-specific CHCHD2 OE, ClpXP protease assay, VEGFA expression and angiogenesis assay, orthotopic HCC mouse model Oncogene Medium 40025232

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 CHCHD2 mutations in autosomal dominant late-onset Parkinson's disease: a genome-wide linkage and sequencing study. The Lancet. Neurology 276 25662902
2017 Loss of Parkinson's disease-associated protein CHCHD2 affects mitochondrial crista structure and destabilizes cytochrome c. Nature communications 142 28589937
2014 MNRR1 (formerly CHCHD2) is a bi-organellar regulator of mitochondrial metabolism. Mitochondrion 138 25315652
2014 CHCHD2 inhibits apoptosis by interacting with Bcl-x L to regulate Bax activation. Cell death and differentiation 97 25476776
2015 CHCHD2 gene mutations in familial and sporadic Parkinson's disease. Neurobiology of aging 67 26705026
2019 Mutations in CHCHD2 cause α-synuclein aggregation. Human molecular genetics 66 31600778
2018 Loss of CHCHD10-CHCHD2 complexes required for respiration underlies the pathogenicity of a CHCHD10 mutation in ALS. Human molecular genetics 65 29121267
2020 Loss of CHCHD2 and CHCHD10 activates OMA1 peptidase to disrupt mitochondrial cristae phenocopying patient mutations. Human molecular genetics 64 32338760
2022 CHCHD2 and CHCHD10 regulate mitochondrial dynamics and integrated stress response. Cell death & disease 63 35173147
2019 PD-linked CHCHD2 mutations impair CHCHD10 and MICOS complex leading to mitochondria dysfunction. Human molecular genetics 58 30496485
2018 The cellular stress proteins CHCHD10 and MNRR1 (CHCHD2): Partners in mitochondrial and nuclear function and dysfunction. The Journal of biological chemistry 57 29540477
2018 CHCHD2 accumulates in distressed mitochondria and facilitates oligomerization of CHCHD10. Human molecular genetics 54 30084972
2015 Mitochondrial targeting sequence variants of the CHCHD2 gene are a risk for Lewy body disorders. Neurology 54 26561290
2015 CHCHD2 Is Coamplified with EGFR in NSCLC and Regulates Mitochondrial Function and Cell Migration. Molecular cancer research : MCR 48 25784717
2019 Twin CHCH Proteins, CHCHD2, and CHCHD10: Key Molecules of Parkinson's Disease, Amyotrophic Lateral Sclerosis, and Frontotemporal Dementia. International journal of molecular sciences 47 30791515
2021 Mitochondrial CHCHD2: Disease-Associated Mutations, Physiological Functions, and Current Animal Models. Frontiers in aging neuroscience 46 33967741
2020 Chchd2 regulates mitochondrial morphology by modulating the levels of Opa1. Cell death and differentiation 42 31907391
2020 Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1) rescues the cellular phenotype of MELAS by inducing homeostatic mechanisms. Proceedings of the National Academy of Sciences of the United States of America 41 33257573
2016 The mitochondrial protein CHCHD2 primes the differentiation potential of human induced pluripotent stem cells to neuroectodermal lineages. The Journal of cell biology 41 27810911
2018 Early-onset Parkinson disease caused by a mutation in CHCHD2 and mitochondrial dysfunction. Neurology. Genetics 40 30338296
2020 ALS and Parkinson's disease genes CHCHD10 and CHCHD2 modify synaptic transcriptomes in human iPSC-derived motor neurons. Neurobiology of disease 30 32437855
2016 Abl2 kinase phosphorylates Bi-organellar regulator MNRR1 in mitochondria, stimulating respiration. Biochimica et biophysica acta. Molecular cell research 28 27913209
2024 Mutant huntingtin impairs neurodevelopment in human brain organoids through CHCHD2-mediated neurometabolic failure. Nature communications 26 39174523
2020 CHCHD2 harboring Parkinson's disease-linked T61I mutation precipitates inside mitochondria and induces precipitation of wild-type CHCHD2. Human molecular genetics 25 32068847
2017 MNRR1, a Biorganellar Regulator of Mitochondria. Oxidative medicine and cellular longevity 25 28685009
2019 Mitochondrial CHCHD2 and CHCHD10: Roles in Neurological Diseases and Therapeutic Implications. The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry 24 31526091
2015 CHCHD2 connects mitochondrial metabolism to apoptosis. Molecular & cellular oncology 22 27308501
2016 Mutational scanning of the CHCHD2 gene in Han Chinese patients with Parkinson's disease and meta-analysis of the literature. Parkinsonism & related disorders 21 27269965
2015 Mutation analysis of CHCHD2 gene in Chinese familial Parkinson's disease. Neurobiology of aging 21 26343503
2022 CHCHD2 p.Thr61Ile knock-in mice exhibit motor defects and neuropathological features of Parkinson's disease. Brain pathology (Zurich, Switzerland) 20 36322611
2015 Cyclic adenosine monophosphate response element-binding protein transcriptionally regulates CHCHD2 associated with the molecular pathogenesis of hepatocellular carcinoma. Molecular medicine reports 20 25625293
2023 CHCHD2 and CHCHD10-related neurodegeneration: molecular pathogenesis and the path to precision therapy. Biochemical Society transactions 19 37021679
2022 Increased CHCHD2 expression promotes liver fibrosis in nonalcoholic steatohepatitis via Notch/osteopontin signaling. JCI insight 19 36477358
2018 CHCHD10 is involved in the development of Parkinson's disease caused by CHCHD2 loss-of-function mutation p.T61I. Neurobiology of aging 19 30530185
2024 CHCHD2 up-regulation in Huntington disease mediates a compensatory protective response against oxidative stress. Cell death & disease 18 38341417
2019 Mitochondrial autoimmunity and MNRR1 in breast carcinogenesis. BMC cancer 18 31046734
2015 Lack of CHCHD2 mutations in Parkinson's disease in a Taiwanese population. Neurobiology of aging 18 26725463
2018 Mutation Screening of the CHCHD2 Gene for Alzheimer's Disease and Frontotemporal Dementia in Chinese Mainland Population. Journal of Alzheimer's disease : JAD 16 29376860
2023 CHCHD2 mediates glioblastoma cell proliferation, mitochondrial metabolism, hypoxia‑induced invasion and therapeutic resistance. International journal of oncology 15 37654190
2015 Mutation analysis of CHCHD2 in Canadian patients with familial Parkinson's disease. Neurobiology of aging 15 26639156
2022 Mouse midbrain dopaminergic neurons survive loss of the PD-associated mitochondrial protein CHCHD2. Human molecular genetics 14 34791217
2015 CHCHD2 is down-regulated in neuronal cells differentiated from iPS cells derived from patients with lissencephaly. Genomics 14 26188257
2022 CCT6A and CHCHD2 Are Coamplified with EGFR and Associated with the Unfavorable Clinical Outcomes of Lung Adenocarcinoma. Disease markers 13 35937942
2022 CHCHD2 and CHCHD10: Future therapeutic targets in cognitive disorder and motor neuron disorder. Frontiers in neuroscience 13 36061599
2025 Dysregulation of mitochondrial α-ketoglutarate dehydrogenase leads to elevated lipid peroxidation in CHCHD2-linked Parkinson's disease models. Nature communications 12 40011434
2024 Neuroprotective role of CHCHD2 in Parkinson's disease: Insights into the GPX4-related ferroptosis pathway. Free radical biology & medicine 12 39566750
2023 Loss of mitochondrial Chchd10 or Chchd2 in zebrafish leads to an ALS-like phenotype and Complex I deficiency independent of the mitochondrial integrated stress response. Developmental neurobiology 12 36799027
2022 CHCHD2 maintains mitochondrial contact site and cristae organizing system stability and protects against mitochondrial dysfunction in an experimental model of Parkinson's disease. Chinese medical journal 12 35830185
2020 CHCHD2 decreases docetaxel sensitivity in breast cancer via activating MMP2. European review for medical and pharmacological sciences 12 32572940
2022 Lipopolysaccharide induces placental mitochondrial dysfunction in murine and human systems by reducing MNRR1 levels via a TLR4-independent pathway. iScience 11 36339251
2023 Involvement of casein kinase 1 epsilon/delta (Csnk1e/d) in the pathogenesis of familial Parkinson's disease caused by CHCHD2. EMBO molecular medicine 10 37578019
2021 Reduced erythrocytic CHCHD2 mRNA is associated with brain pathology of Parkinson's disease. Acta neuropathologica communications 10 33685516
2018 Knockdown of CHCHD2 inhibits migration and angiogenesis of human renal cell carcinoma: A potential molecular marker for treatment of RCC. Oncology letters 10 30655828
2016 Genetic analysis of CHCHD2 gene in Chinese Parkinson's disease. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 10 27626775
2022 CHCHD2 Regulates Mitochondrial Function and Apoptosis of Ectopic Endometrial Stromal Cells in the Pathogenesis of Endometriosis. Reproductive sciences (Thousand Oaks, Calif.) 9 35157262
2022 Pathological characterization of a novel mouse model expressing the PD-linked CHCHD2-T61I mutation. Human molecular genetics 9 35786718
2018 Mutation analysis of CHCHD2 and CHCHD10 in Italian patients with mitochondrial myopathy. Neurobiology of aging 9 29519717
2016 Mutation analysis of CHCHD2 gene in Chinese Han familial essential tremor patients and familial Parkinson's disease patients. Neurobiology of aging 9 27814991
2016 Analysis of CHCHD2 gene in familial Parkinson's disease from Calabria. Neurobiology of aging 9 27839905
2023 MNRR1 is a driver of ovarian cancer progression. Translational oncology 8 36641875
2024 Aberrant CHCHD2-associated mitochondriopathy in Kii ALS/PDC astrocytes. Acta neuropathologica 7 38750212
2018 Identification of CHCHD2 mutations in patients with Alzheimer's disease, amyotrophic lateral sclerosis and frontotemporal dementia in China. Molecular medicine reports 7 29749507
2018 Generation of induced pluripotent stem cell line (ZZUi007-A) from a 52-year-old patient with a novel CHCHD2 gene mutation in Parkinson's disease. Stem cell research 7 30237140
2017 Genetic analysis of CHCHD2 and CHCHD10 in Italian patients with Parkinson's disease. Neurobiology of aging 7 28108040
2016 Genetic analysis of CHCHD2 in a southern Spanish population. Neurobiology of aging 7 27839904
2024 CHCHD2 Thr61Ile mutation impairs F1F0-ATPase assembly in in vitro and in vivo models of Parkinson's disease. Neural regeneration research 6 37488867
2016 Genetic analysis of the CHCHD2 gene in a cohort of Chinese patients with Parkinson disease. Neuroscience letters 6 27353515
2024 Loss of CHCHD2 Stability Coordinates with C1QBP/CHCHD2/CHCHD10 Complex Impairment to Mediate PD-Linked Mitochondrial Dysfunction. Molecular neurobiology 5 38453793
2023 The CHCHD2/Sirt1 corepressors involve in G9a-mediated regulation of RNase H1 expression to control R-loop. Cell insight 5 37388553
2020 Mitochondria Autoimmunity and MNRR1 in Breast Carcinogenesis: A Review. Journal of cancer immunology 5 33615312
2018 CHCHD2 mutational screening in Brazilian patients with familial Parkinson's disease. Neurobiology of aging 5 30342766
2016 Genetic analysis of the CHCHD2 gene in Chinese patients with familial essential tremor. Neuroscience letters 5 27717833
2025 LncRNA MALAT1 Facilitates HIV-1 Replication by Upregulation of CHCHD2 and Downregulation of IFN-I Expression. Molecular & cellular proteomics : MCP 4 40414289
2024 Epigenetic repression of CHCHD2 enhances survival from single cell dissociation through attenuated Rho A kinase activity. Cellular and molecular life sciences : CMLS 4 38214772
2024 Genetic and pharmacologic p32-inhibition rescue CHCHD2-linked Parkinson's disease phenotypes in vivo and in cell models. Journal of biomedical science 4 38395904
2024 Resonance Raman spectral analysis of the heme site structure of cytochrome c oxidase with its positive regulator CHCHD2. Journal of inorganic biochemistry 4 39094247
2023 What is the role of CHCHD2 in adrenal tumourigenesis? Endocrine 4 37221428
2023 Clinical chorioamnionitis at term is characterized by changes in the plasma concentration of CHCHD2/MNRR1, a mitochondrial protein. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 4 37349086
2025 CHCHD2 rescues the mitochondrial dysfunction in iPSC-derived neurons from patient with Mohr-Tranebjaerg syndrome. Cell death & disease 3 40075073
2024 CHCHD2 mutant mice display mitochondrial protein accumulation and disrupted energy metabolism. bioRxiv : the preprint server for biology 3 39257750
2023 Evidence for the participation of CHCHD2/MNRR1, a mitochondrial protein, in spontaneous labor at term and in preterm labor with intra-amniotic infection. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 3 36941246
2022 Downregulation of CHCHD2 may Contribute to Parkinson's Disease by Reducing Expression of NFE2L2 and RQCD1. Current neurovascular research 3 35388756
2018 [Value of CHCHD2 as a potential marker of non-small cell lung cancer: analysis of 60 cases]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 3 29643040
2025 Impaired mitochondrial degradation of CHCHD2 promotes metabolic dysfunction-associated steatohepatitis-related hepatocellular carcinoma by upregulating VEGFA. Oncogene 2 40025232
2025 CHCHD2 mutant mice link mitochondrial deficits to PD pathophysiology. Science advances 2 41237231
2024 A mitochondrial regulator protein, MNRR1, is elevated in the maternal blood of women with preeclampsia. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 2 38220225
2022 Production of a human iPSC line from an early-onset Parkinson's disease patient with a novel CHCHD2 gene truncated mutation. Stem cell research 2 35944313
2025 Therapeutic Potential of CHCHD2 in Ischemia-Reperfusion Injury: Mechanistic Insights into Nrf2-Dependent Antioxidant Defense in HK2 Cells. International journal of molecular sciences 1 40649864
2025 Cortical organoids reveal human-specific roles of METTL5 in neurodevelopment via regulation of CHCHD2. bioRxiv : the preprint server for biology 1 40672170
2025 Pseudohypoxia-Stabilized HIF2α Transcriptionally Inhibits MNRR1, a Druggable Target in MELAS. Cells 1 40710331
2025 The CHCHD2-CHCHD10 protein complex is modulated by mitochondrial dysfunction and alters lipid homeostasis in the mouse brain. Cell death & disease 1 41053020
2026 Transcriptional activation by MNRR1 is effected by recruiting p300 and can be induced by minimal peptides. Mitochondrion 0 41592630
2026 CHCHD2, Rather than FBXO7, Plays an Essential Role in Modulating the MPP+-Induced mtUPR. ACS chemical neuroscience 0 41640382
2026 Gamabufotalin impedes NSCLC progression by inhibiting the mitochondrial factor CHCHD2 and modulating XAF1 expression. Biochemical pharmacology 0 41692347
2026 CHCHD2 links mitochondrial dysfunction and α-synuclein misfolding in Parkinson's disease. Trends in neurosciences 0 41763921
2026 CHCHD2: a bi-organellar fulcrum of mitochondrial homeostasis and reproductive pathology. European journal of obstetrics, gynecology, and reproductive biology 0 41996908
2026 CHCHD2 and CHCHD10 promoted autophagic clearance of protein aggregates via GABARAPs. Autophagy 0 42183628
2025 Role of the mitochondrial regulatory factor CHCHD2 in neurodegenerative diseases. Frontiers in neuroscience 0 40963812
2024 Generation of a human iPSC line from a Parkinson's disease patient with a novel CHCHD2 mutation (p.R145Q). Stem cell research 0 38631182
2023 D130A variant on Parkinson 22-related CHCHD2 is predicted to have decreased protein movement. microPublication biology 0 38188421

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