Affinage

CHCHD10

Coiled-coil-helix-coiled-coil-helix domain-containing protein 10, mitochondrial · UniProt Q8WYQ3

Length
142 aa
Mass
14.1 kDa
Annotated
2026-04-28
83 papers in source corpus 28 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CHCHD10 is a mitochondrial intermembrane space protein that maintains cristae architecture, oxidative phosphorylation, and mitochondrial DNA stability by functioning within the MICOS complex and as a heterodimer with its paralog CHCHD2. It interacts with cytochrome c oxidase (Complex IV) to scaffold COX activity, suppresses OMA1 protease activity to preserve long-form OPA1 and cristae junctions, and interacts with PARL to sustain PINK1-dependent mitophagy flux; during mitochondrial stress, CHCHD10 translocates to the cytosol to attenuate integrated stress response signaling by suppressing eIF2α phosphorylation (PMID:26666268, PMID:35173147, PMID:29540477, PMID:38132101). Disease-associated mutations (e.g., S59L, R15L, G58R) act primarily through toxic gain-of-function aggregation that disrupts IMS proteostasis, activates the OMA1–DELE1–HRI stress axis, impairs cytochrome c biogenesis, and promotes cytoplasmic TDP-43 mislocalization, whereas complete loss of CHCHD10 alone does not recapitulate disease but impairs Complex I assembly and ATP-dependent processes including neuromuscular junction maintenance and adipocyte thermogenesis (PMID:30877432, PMID:35700042, PMID:41420107, PMID:31261376, PMID:35709007). Mutations in CHCHD10 cause frontotemporal dementia–amyotrophic lateral sclerosis spectrum disease and motor neuron disease (PMID:24934289, PMID:29315381).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2010 Medium

    Establishing that CHCHD10 participates in oxidative phosphorylation answered the basic question of what this uncharacterized CHCH-domain protein does: it is required for Complex IV activity.

    Evidence siRNA knockdown with Complex IV activity assay in vitro

    PMID:20888800

    Open questions at the time
    • Single lab, single complex assayed
    • No mechanism for how CHCHD10 supports Complex IV identified
    • Broader OXPHOS roles not tested
  2. 2014 High

    Localization of CHCHD10 to the intermembrane space at cristae junctions and demonstration that the S59L mutation disrupts cristae established the protein as a structural organizer of mitochondrial inner membrane architecture and linked it to FTD-ALS.

    Evidence Immunofluorescence, subcellular fractionation, and electron microscopy of S59L-overexpressing HeLa cells; genetic linkage in FTD-ALS family

    PMID:24934289

    Open questions at the time
    • Endogenous complex membership not yet identified
    • Whether loss-of-function or gain-of-function drives disease was unknown
  3. 2016 High

    Identification of CHCHD10 as a component of the MICOS complex (with mitofilin, CHCHD3, CHCHD6) explained how it organizes cristae junctions and revealed that disease mutations cause MICOS disassembly, nucleoid loss, and impaired mtDNA repair.

    Evidence Co-immunoprecipitation in patient fibroblasts, electron microscopy, nucleoid staining, cytochrome c release assay

    PMID:26666268

    Open questions at the time
    • Direct structural contacts within MICOS not resolved
    • Whether CHCHD10 is a core or peripheral MICOS subunit unclear
  4. 2017 High

    Demonstration that CHCHD10 promotes nuclear retention of TDP-43 and that disease mutations cause cytoplasmic TDP-43 mislocalization connected mitochondrial dysfunction to a hallmark of ALS/FTD pathology.

    Evidence C. elegans genetic complementation, mammalian cell overexpression, primary neuron and mouse brain TDP-43 localization

    PMID:28585542

    Open questions at the time
    • Mechanism by which CHCHD10 retains TDP-43 in the nucleus not identified
    • Whether TDP-43 mislocalization is a cause or consequence of mitochondrial damage unclear
  5. 2018 High

    Multiple studies converged to define CHCHD10's molecular partnerships and biogenesis: it forms heterodimers with CHCHD2 in a stress-responsive ~220 kDa complex, interacts with p32/C1QBP, scaffolds COX activity via CHCHD2/ABL2, and requires Mia40-dependent disulfide bond formation for mitochondrial import; disease mutations disrupt these interactions through distinct mechanisms (import failure, destabilization, or aberrant binding).

    Evidence Co-IP/MS interactome, BN-PAGE, COX co-purification and activity assay, Mia40 knockdown/rescue, truncation mutagenesis, zebrafish knockdown, patient fibroblasts, multiple disease mutants tested across labs

    PMID:29112723 PMID:29121267 PMID:29315381 PMID:29540477 PMID:29789341 PMID:30084972

    Open questions at the time
    • Stoichiometry of the ~220 kDa complex not determined
    • Whether nuclear CHCHD10-CXXC5 interaction is physiologically significant in vivo unclear
    • Structural basis of heterodimer formation unknown
  6. 2019 High

    Comparison of S55L knock-in versus CHCHD10-knockout mice resolved the disease mechanism debate: mutant protein aggregates activate mtISR via mTORC1 in a toxic gain-of-function manner, while knockout alone does not cause neurodegeneration; separately, muscle-conditional knockout revealed that CHCHD10 maintains neuromuscular junction integrity through ATP-dependent AChR clustering.

    Evidence Knock-in vs. knockout mouse comparison, aggregation analysis, transcriptomics/metabolomics, muscle-conditional KO with electrophysiology and ATP rescue

    PMID:30874923 PMID:30877432 PMID:31261376

    Open questions at the time
    • Why aggregate toxicity is tissue-selective not explained
    • Whether gain-of-function and haploinsufficiency mechanisms coexist for different mutations not fully resolved
  7. 2020 High

    Identification of OMA1-mediated L-OPA1 cleavage as the effector of cristae disruption in CHCHD2/CHCHD10 double-knockout mice provided the first enzymatic mechanism linking CHCHD10 loss to mitochondrial fragmentation, and revealed that TDP-43 overexpression itself reduces CHCHD10 levels to disrupt OPA1-mitofilin complexes.

    Evidence CHCHD2/CHCHD10 double-KO mice, OMA1 activation and OPA1 cleavage assays, Co-IP in FTLD-TDP patient brain, CHCHD10 overexpression rescue

    PMID:32338760 PMID:32369233

    Open questions at the time
    • How CHCHD10 inhibits OMA1 at the molecular level unknown
    • Whether OPA1-mitofilin disruption is the primary driver or one of several parallel cascades uncertain
  8. 2021 High

    Multi-omics of R15L patient fibroblasts revealed that Complex I deficiency drives a metabolic cascade (elevated NADH/NAD+, AMPK activation, mTORC1 inhibition, UPR activation), while Drosophila/cell studies showed that S59L activates TDP-43 and PINK1 pathways independently, with pharmacological PINK1 modulation providing rescue.

    Evidence Integrated transcriptomics/metabolomics/proteomics in patient fibroblasts, Drosophila transgenic model with PINK1 genetic/pharmacological epistasis, TDP-43 mitochondrial import inhibitor peptide

    PMID:33749723 PMID:33772006

    Open questions at the time
    • Whether PINK1 pathway activation is protective or pathogenic across all mutation types not established
    • Therapeutic potential of TDP-43 import inhibition not tested in mammalian models
  9. 2022 High

    The OMA1–DELE1–HRI signaling axis was identified as both a pathogenic output and a protective response in CHCHD10 disease: CHCHD10/CHCHD2 normally suppress OMA1 and cytosolic eIF2α phosphorylation, while OMA1-dependent DELE1 cleavage is required for survival of G58R knock-in mice; simultaneously, S59L aggregates destabilize the SLP2-prohibitin complex upstream of OMA1, and WT CHCHD10 directly inhibits TDP-43 aggregation in reconstituted systems.

    Evidence Co-IP with OMA1 and SLP2/PHB, OMA1 KO genetic cross in KI mice, DELE1 cleavage assay, eIF2α phosphorylation, cell-free TDP-43 aggregation with atomic force microscopy

    PMID:35173147 PMID:35656794 PMID:35700042 PMID:35787294

    Open questions at the time
    • Whether OMA1 suppression and mtISR attenuation are independent or sequential functions of CHCHD10 not resolved
    • Direct binding interface between CHCHD10 and OMA1 not structurally defined
  10. 2023 High

    Discovery that CHCHD10 interacts with PARL to suppress its protease activity, thereby sustaining PINK1 for mitophagy, provided the mechanistic link between CHCHD10 mutations and impaired mitophagy flux that promotes TDP-43 aggregation.

    Evidence Co-IP with PARL, PINK1 level measurement, mitophagy flux and Parkin recruitment assays in mouse and human FTD brain

    PMID:38132101

    Open questions at the time
    • Whether PARL interaction is direct or mediated through the PHB/SLP2 platform not determined
    • Relative contribution of impaired mitophagy vs. direct aggregation to TDP-43 pathology unclear
  11. 2025 High

    The pathogenic cascade was further refined: mutant CHCHD10 disrupts IMS copper homeostasis and cytochrome c biogenesis, and exogenous cytochrome c rescues respiration, pinpointing IMS proteostasis failure as a proximal cause; OMA1 catalytic blunting delays cardiomyopathy but does not rescue OXPHOS, separating the stress-signaling and bioenergetic arms of disease.

    Evidence Knock-in mouse proteomic profiling, cytochrome c biochemical rescue of respiration, OMA1 E324Q catalytic mutant cross

    PMID:41420107

    Open questions at the time
    • How mutant CHCHD10 specifically impairs copper delivery or cytochrome c maturation not resolved
    • Whether IMS proteostasis disruption is reversible therapeutically not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic-resolution structure of the CHCHD10-CHCHD2 heterodimer and its interfaces with OMA1, PARL, and MICOS components; the basis for tissue-selective vulnerability in gain-of-function disease; and whether therapeutic strategies targeting OMA1, PINK1, or TDP-43 mitochondrial import can modify disease course in mammalian models.
  • No high-resolution structure of the CHCHD10-CHCHD2 complex or its interaction interfaces
  • Tissue-selective vulnerability mechanism unexplained
  • No preclinical therapeutic efficacy data in mammalian ALS/FTD models

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005739 mitochondrion 4 GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 6 R-HSA-8953897 Cellular responses to stimuli 5 R-HSA-1852241 Organelle biogenesis and maintenance 4 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 1
Partners
C1QBPCHCHD2CHCHD3CHCHD6IMMTOMA1PARLSLP2
Complex memberships
CHCHD10-CHCHD2 heterodimerMICOS complexSLP2-prohibitin complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 CHCHD10 is a mitochondrial protein localized to the intermembrane space and enriched at cristae junctions; overexpression of the S59L mutant allele causes fragmentation of the mitochondrial network and ultrastructural abnormalities including loss, disorganization, and dilatation of cristae in HeLa cells. Immunofluorescence, subcellular fractionation, electron microscopy, overexpression of mutant allele in HeLa cells Brain High 24934289
2016 CHCHD10 resides within the MICOS (mitochondrial contact site and cristae organizing system) complex together with mitofilin, CHCHD3, and CHCHD6; disease-associated CHCHD10 mutations lead to MICOS complex disassembly, loss of cristae, decreased nucleoid number, impaired mtDNA repair after oxidative stress, and inhibition of apoptosis by preventing cytochrome c release. Co-immunoprecipitation, patient fibroblast analysis, electron microscopy, nucleoid staining, cytochrome c release assay EMBO molecular medicine High 26666268
2010 CHCHD10 knockdown reduces Complex IV (cytochrome c oxidase) activity in vitro, establishing a role for CHCHD10 in oxidative phosphorylation. siRNA knockdown, complex IV activity assay Biochemical and biophysical research communications Medium 20888800
2018 CHCHD10 associates with membranes in the mitochondrial intermembrane space and directly interacts with its paralog CHCHD2 and with p32/C1QBP; CHCHD10 has a short half-life suggesting a regulatory role; knockdown leads to intramitochondrial iron accumulation; S59L and R15L mutants (but not WT) impair mitochondrial energy metabolism. Immunoprecipitation/MS interactome, subcellular fractionation, pulse-chase half-life assays, iron measurement, Seahorse bioenergetics, knockout mice Human molecular genetics High 29112723
2018 The p.R15L CHCHD10 variant destabilizes the protein and causes defective assembly of mitochondrial Complex I, impaired cellular respiration, and mitochondrial hyperfusion; CHCHD10 and CHCHD2 form a high molecular weight complex (~220 kDa) by blue native PAGE that is absent in patient cells. Blue native PAGE, immunoprecipitation, oxygen consumption measurement, patient fibroblasts, galactose growth assay Human molecular genetics High 29121267
2018 Mitochondrial import of CHCHD10 is mediated by the CHCH domain rather than the N-terminal targeting signal and depends on Mia40, which introduces disulfide bonds; the Q108P disease mutation nearly completely blocks mitochondrial import, resulting in cytoplasmic mislocalization; Mia40 overexpression rescues import of CHCHD10 Q108P. Truncation mutagenesis, Mia40 knockdown/overexpression, immunofluorescence localization, cycloheximide stability assay EMBO molecular medicine High 29789341
2018 CHCHD2 and CHCHD10 form heterodimers that increase in response to mitochondrial stress; CHCHD2 is preferentially stabilized upon loss of mitochondrial membrane potential, and CHCHD10 oligomerization depends on CHCHD2 expression; disease-causing mutations in both proteins can be incorporated into heterodimers. CHCHD2/CHCHD10 double-knockout cell lines, co-immunoprecipitation, immunofluorescence, CCCP treatment, heterodimer incorporation assay Human molecular genetics High 30084972
2018 CHCHD10 copurifies with cytochrome c oxidase (Complex IV) and up-regulates COX activity by acting as a scaffolding protein required for MNRR1/CHCHD2 phosphorylation mediated by ABL2 kinase; nuclear CHCHD10 interacts with the transcriptional repressor CXXC5 and down-regulates expression of genes with oxygen-responsive elements (ORE) in their promoters; disease variants G66V and P80L exhibit faulty interactions with MNRR1 and COX, reducing respiration and increasing ROS. Co-purification/Co-IP with COX, COX activity assay, nuclear fractionation, reporter gene assay, ROS measurement, Seahorse bioenergetics The Journal of biological chemistry High 29540477
2019 CHCHD10 S55L (mouse equivalent of human S59L) knock-in mice accumulate CHCHD10/CHCHD2 aggregates specifically in affected tissues, leading to aberrant organelle morphology and activation of a mitochondrial integrated stress response (mtISR) through mTORC1; CHCHD10 ablation does not induce disease pathology or activate mtISR, indicating that S55L disease is caused by a toxic gain-of-function rather than loss-of-function. Knock-in mouse model, protein aggregation analysis (fractionation/IF), electron microscopy, transcriptomic/metabolomic profiling, mTORC1 pathway analysis, CHCHD10 knockout comparison Acta neuropathologica High 30877432
2020 Loss of both CHCHD2 and CHCHD10 (double knockout mice) disrupts mitochondrial cristae through OMA1-mediated cleavage of long-form OPA1 (L-OPA1); OMA1 is similarly activated in affected tissues of mutant CHCHD10 knock-in mice; C2/C10 DKO mice develop cardiomyopathy and activate the mtISR, partially phenocopying mutant C10 KI mice. CHCHD2/CHCHD10 double-knockout mice, OMA1 activation assay, OPA1 cleavage by western blot, electron microscopy, knock-in mouse comparison Human molecular genetics High 32338760
2022 CHCHD2 and CHCHD10 interact with OMA1 and suppress its protease activity under physiological conditions, restraining both mtISR initiation and OPA1 processing for mitochondrial fusion; during mitochondrial stress (CCCP), CHCHD2 and CHCHD10 translocate to the cytosol and interact with eIF2α, attenuating mtISR overactivation by suppressing eIF2α phosphorylation. Co-immunoprecipitation with OMA1, OPA1 cleavage assay, CCCP treatment, cytosol/mitochondria fractionation, eIF2α phosphorylation measurement, CHCHD2/CHCHD10 knockdown Cell death & disease High 35173147
2022 OMA1 mediates a protective stress response in CHCHD10 G58R mutant knock-in mice by acting both locally (mitochondrial fragmentation) and globally (cleavage of DELE1 to activate the integrated stress response); survival of CHCHD10-KI mice depends on this OMA1-mediated response; an isoform switch in the terminal complex of the electron transport chain also occurs as part of this response. Knock-in mouse model, OMA1 knockout cross, DELE1 cleavage assay, electron microscopy, transcriptomic profiling The Journal of clinical investigation High 35700042
2022 CHCHD10 interacts with SLP2 (Stomatin-Like Protein 2) and participates in the stability of the prohibitin (PHB) complex in the inner mitochondrial membrane; CHCHD10 S59L mutation causes SLP2 and prohibitins to form aggregates, destabilizing the PHB complex, which activates OMA1 leading to OPA1 processing, mitochondrial fragmentation, and neuronal death; this also destabilizes the MICOS complex through disruption of OPA1-mitofilin interaction. Co-immunoprecipitation, patient fibroblasts and knock-in mouse tissue analysis, immunofluorescence, electron microscopy, OPA1 cleavage assay Brain High 35656794
2019 CHCHD10 is highly expressed at the postsynaptic NMJ in skeletal muscle; muscle-conditional CHCHD10 knockout mice exhibit motor defects, abnormal neuromuscular transmission, and disrupted NMJ structure; mechanistically, CHCHD10 is required for mitochondrial ATP production, which facilitates AChR expression and promotes agrin-induced AChR clustering; exogenous ATP rescues AChR cluster reduction. Muscle-conditional knockout mice, electrophysiology, AChR clustering assay, ATP rescue experiment, immunofluorescence Human molecular genetics High 31261376
2017 CHCHD10 normally promotes retention of nuclear TDP-43, protects mitochondrial and synaptic integrity; FTD/ALS mutations R15L and S59L exhibit loss-of-function phenotypes in C. elegans genetic complementation assays and dominant-negative activities in mammalian systems, resulting in mitochondrial/synaptic damage and cytoplasmic TDP-43 accumulation. C. elegans genetic complementation assay, mammalian cell overexpression, primary neurons, mouse brain analysis, TDP-43 localization Nature communications High 28585542
2021 The p.R15L CHCHD10 variant (haploinsufficient) causes Complex I deficiency resulting in elevated NADH/NAD+ ratio, diminished TCA cycle activity, reorganization of one-carbon metabolism, increased AMP/ATP ratio leading to AMPK phosphorylation and mTORC1 inhibition; these metabolic changes activate UPR in the ER (IRE1/XBP1 pathway) and the mitochondrial UPR through ATF4/ATF5 upregulation. Multi-OMICS (transcriptomics, metabolomics, proteomics) in patient fibroblasts under energetic stress, pathway analysis Human molecular genetics High 33749723
2019 CHCHD10 S59L knock-in mice develop OXPHOS deficiency in muscle at 3 months before neuromuscular junction degeneration and motor neuron loss, establishing that muscle pathology precedes neurodegeneration; TDP-43 cytoplasmic aggregates appear in spinal neurons at late disease stage; iPSC-derived motor neurons with S59L are more sensitive to caspase activation. Knock-in mouse model, histochemistry (OXPHOS), NMJ morphology, motor neuron counting, TDP-43 immunostaining, iPSC-derived motor neuron caspase assay Acta neuropathologica High 30874923
2021 In Drosophila and HeLa cells, CHCHD10 S59L independently activates the TDP-43 and PINK1 pathways: S59L increases TDP-43 insolubility and mitochondrial translocation; blocking TDP-43 mitochondrial translocation with a peptide inhibitor reduces S59L-mediated toxicity; genetic and pharmacological modulation of PINK1 rescues S59L-induced phenotypes. Drosophila transgenic model, HeLa cell overexpression, peptide inhibitor of TDP-43 import, PINK1 genetic and pharmacological modulation, mitochondrial fractionation Nature communications High 33772006
2020 CHCHD10 mutations disrupt mitochondrial OPA1-mitofilin complexes in brain, impairing mitochondrial fusion and respiration; CHCHD10 knockdown causes OPA1-mitofilin complex disassembly; TDP-43 overexpression reduces CHCHD10 levels and promotes OPA1-mitofilin disassembly via CHCHD10, and WT CHCHD10 overexpression rescues these defects. Co-immunoprecipitation, CHCHD10 knockdown/overexpression, mitochondrial fusion assay, Seahorse respiration, FTLD-TDP patient brain analysis FASEB journal High 32369233
2023 CHCHD10 normally interacts with PARL, suppressing its activity, which sustains PINK1 levels and promotes mitophagy flux and Parkin recruitment; CHCHD10 R15L and S59L mutations reduce PINK1 levels by increasing PARL activity; impaired mitophagy promotes TDP-43 aggregation. Co-immunoprecipitation with PARL, PINK1 level measurement, mitophagy flux assay, Parkin recruitment assay, in vivo mouse and human FTD brain tissue Cells High 38132101
2018 CHCHD10 G66V and P80L mutations cause motoneuron disease primarily through haploinsufficiency: p.R15L reduces CHCHD10 mRNA expression, while p.G66V results in altered protein secondary structure and rapid degradation, reducing protein levels to ~50%; knockdown of CHCHD10 to ~50% in zebrafish causes motoneuron pathology, abnormal myofibrillar structure, and motility deficits. Patient cell protein/mRNA quantification, secondary structure analysis, zebrafish knockdown model, motor behavior assay Human molecular genetics High 29315381
2022 CHCHD10 S59L mutant protein induces aggregation of resident CHCHD10 and promotes aggregation and slower turnover of imported TDP-43 in isolated mitochondria; in a cell-free system, S59L CHCHD10 enhances TDP-43 aggregation while WT CHCHD10 inhibits TDP-43 aggregate growth, as shown by filter trap assay and atomic force microscopy. Isolated mitochondria import assay, cell-free aggregation assay, filter trap, atomic force microscopy, transgenic mouse brain analysis Acta neuropathologica communications High 35787294
2025 Mutant CHCHD10 (S55L/S59L) causes dual defects: (1) impaired mitochondrial copper homeostasis leading to defective cytochrome c oxidation, and (2) maladaptive mtISR signaling via the OMA1-DELE1-HRI axis; defective respiration in mutant mitochondria is rescued by exogenous addition of cytochrome c, implicating IMS proteostasis disruption as a key pathogenic mechanism; blunting OMA1 activity (Oma1 E324Q KI) delays cardiomyopathy without rescuing OXPHOS impairment. Knock-in mouse models, proteomic profiling (soluble/insoluble fractions), cytochrome c rescue of respiration, OMA1 catalytic mutant cross, DELE1 cleavage assay EMBO molecular medicine High 41420107
2022 CHCHD10 deficiency in adipocytes disrupts mitochondrial cristae and OXPHOS complex assembly, impairing ATP generation; decreased ATP reduces lipolysis by lowering nascent ATGL protein synthesis, thereby suppressing UCP1-dependent thermogenesis; ATGL overexpression rescues thermogenesis in CHCHD10-knockout adipocytes. Adipocyte-specific CHCHD10 knockout mice, UCP1/ATP measurement, lipolysis assay, ATGL overexpression rescue, Seahorse bioenergetics Diabetes High 35709007
2019 CHCHD2 T61I mutation causes increased interaction between CHCHD2 and CHCHD10, leading to reduced CHCHD10 levels; mitochondrial ultrastructural alterations in CHCHD2 T61I patient fibroblasts resemble those of CHCHD10 mutation cells. Co-immunoprecipitation, CHCHD10 protein level measurement, patient fibroblast electron microscopy Neurobiology of aging Medium 30530185
2024 The N-terminal disordered domain of CHCHD10 forms amyloid fibrils whose cryo-EM structure shows that disease-associated mutations cannot be accommodated by the WT fibril structure, while sequence differences between CHCHD10 and CHCHD2 are tolerated, explaining their co-aggregation. CryoEM structure determination, amyloid fibril formation assay, mutant accommodation modeling bioRxiv (preprint)preprint Medium
2025 CHCHD2 and CHCHD10 exist in mouse tissues as a high molecular weight complex whose levels increase in response to mitochondrial dysfunction; loss of CHCHD2 enhances cellular vulnerability to mitochondrial stress; CHCHD2 is required for normal striatal dopamine levels and lipid homeostasis in mouse brain. Chchd2 knockout mouse, BN-PAGE complex analysis, mitochondrial stress treatments, dopamine measurement, lipidomics Cell death & disease Medium 41053020
2023 Loss of chchd10 (but not chchd2) in zebrafish impairs assembly of mitochondrial respiratory Complex I; in double chchd10/chchd2 knockout zebrafish, Complex I impairment is unexpectedly restored via mtISR transcriptional activation, showing that the mt-ISR can compensate for Complex I deficiency. Zebrafish knockout models (single and double), Complex I assembly BN-PAGE, mt-ISR transcriptional markers, motor behavior assay Developmental neurobiology Medium 36799027
2025 CHCHD10 deficiency in adipose tissue enhances adipogenesis and GSTA4 expression by activating a TDP43/Raptor/p62/Keap1/NRF2 axis; in hypertrophic adipocytes where p62 is reduced, this beneficial effect is eliminated. AT-specific Chchd10 KO mice, co-IP/pathway analysis, p62 manipulation, NRF2 reporter assay Advanced science Medium 39985288

Source papers

Stage 0 corpus · 83 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 A mitochondrial origin for frontotemporal dementia and amyotrophic lateral sclerosis through CHCHD10 involvement. Brain : a journal of neurology 406 24934289
2016 CHCHD10 mutations promote loss of mitochondrial cristae junctions with impaired mitochondrial genome maintenance and inhibition of apoptosis. EMBO molecular medicine 159 26666268
2014 Screening of CHCHD10 in a French cohort confirms the involvement of this gene in frontotemporal dementia with amyotrophic lateral sclerosis patients. Neurobiology of aging 113 25155093
2014 Mutation in the novel nuclear-encoded mitochondrial protein CHCHD10 in a family with autosomal dominant mitochondrial myopathy. Neurogenetics 100 25193783
2017 Loss of function CHCHD10 mutations in cytoplasmic TDP-43 accumulation and synaptic integrity. Nature communications 98 28585542
2014 Late onset spinal motor neuronopathy is caused by mutation in CHCHD10. Annals of neurology 94 25428574
2018 In vitro and in vivo studies of the ALS-FTLD protein CHCHD10 reveal novel mitochondrial topology and protein interactions. Human molecular genetics 88 29112723
2019 ALS/FTD mutant CHCHD10 mice reveal a tissue-specific toxic gain-of-function and mitochondrial stress response. Acta neuropathologica 84 30877432
2019 Mitochondrial defect in muscle precedes neuromuscular junction degeneration and motor neuron death in CHCHD10S59L/+ mouse. Acta neuropathologica 78 30874923
2015 CHCHD10 variant p.(Gly66Val) causes axonal Charcot-Marie-Tooth disease. Neurology. Genetics 71 27066538
2018 Loss of CHCHD10-CHCHD2 complexes required for respiration underlies the pathogenicity of a CHCHD10 mutation in ALS. Human molecular genetics 64 29121267
2020 Loss of CHCHD2 and CHCHD10 activates OMA1 peptidase to disrupt mitochondrial cristae phenocopying patient mutations. Human molecular genetics 63 32338760
2022 CHCHD2 and CHCHD10 regulate mitochondrial dynamics and integrated stress response. Cell death & disease 61 35173147
2016 Investigating the role of ALS genes CHCHD10 and TUBA4A in Belgian FTD-ALS spectrum patients. Neurobiology of aging 59 28069311
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
2022 OMA1 mediates local and global stress responses against protein misfolding in CHCHD10 mitochondrial myopathy. The Journal of clinical investigation 53 35700042
2018 CHCHD2 accumulates in distressed mitochondria and facilitates oligomerization of CHCHD10. Human molecular genetics 53 30084972
2018 Loss of MICOS complex integrity and mitochondrial damage, but not TDP-43 mitochondrial localisation, are likely associated with severity of CHCHD10-related diseases. Neurobiology of disease 53 30092269
2021 Multi-OMICS study of a CHCHD10 variant causing ALS demonstrates metabolic rewiring and activation of endoplasmic reticulum and mitochondrial unfolded protein responses. Human molecular genetics 52 33749723
2019 Twin CHCH Proteins, CHCHD2, and CHCHD10: Key Molecules of Parkinson's Disease, Amyotrophic Lateral Sclerosis, and Frontotemporal Dementia. International journal of molecular sciences 46 30791515
2018 A novel CHCHD10 mutation implicates a Mia40-dependent mitochondrial import deficit in ALS. EMBO molecular medicine 45 29789341
2020 Loss of mitochondrial protein CHCHD10 in skeletal muscle causes neuromuscular junction impairment. Human molecular genetics 36 31261376
2010 Functional annotation of heart enriched mitochondrial genes GBAS and CHCHD10 through guilt by association. Biochemical and biophysical research communications 36 20888800
2020 CHCHD10-regulated OPA1-mitofilin complex mediates TDP-43-induced mitochondrial phenotypes associated with frontotemporal dementia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 33 32369233
2018 CHCHD10 mutations p.R15L and p.G66V cause motoneuron disease by haploinsufficiency. Human molecular genetics 33 29315381
2017 Genetic Features of MAPT, GRN, C9orf72 and CHCHD10 Gene Mutations in Chinese Patients with Frontotemporal Dementia. Current Alzheimer research 31 28462717
2020 ALS and Parkinson's disease genes CHCHD10 and CHCHD2 modify synaptic transcriptomes in human iPSC-derived motor neurons. Neurobiology of disease 30 32437855
2022 Mutant CHCHD10 causes an extensive metabolic rewiring that precedes OXPHOS dysfunction in a murine model of mitochondrial cardiomyopathy. Cell reports 25 35263592
2022 CHCHD10 and SLP2 control the stability of the PHB complex: a key factor for motor neuron viability. Brain : a journal of neurology 25 35656794
2018 CHCHD10 variants in amyotrophic lateral sclerosis: Where is the evidence? Annals of neurology 25 30014597
2019 Mitochondrial CHCHD2 and CHCHD10: Roles in Neurological Diseases and Therapeutic Implications. The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry 24 31526091
2022 Modulation of synaptic plasticity, motor unit physiology, and TDP-43 pathology by CHCHD10. Acta neuropathologica communications 23 35787294
2020 Neuropathologic description of CHCHD10 mutated amyotrophic lateral sclerosis. Neurology. Genetics 23 32042922
2015 Intrafamilial clinical variability in individuals carrying the CHCHD10 mutation Gly66Val. Acta neurologica Scandinavica 23 26224640
2021 TDP-43 and PINK1 mediate CHCHD10S59L mutation-induced defects in Drosophila and in vitro. Nature communications 22 33772006
2016 Mutation Screening of the CHCHD10 Gene in Chinese Patients with Amyotrophic Lateral Sclerosis. Molecular neurobiology 21 27056076
2016 Identification of CHCHD10 Mutation in Chinese Patients with Alzheimer Disease. Molecular neurobiology 21 27578015
2023 CHCHD2 and CHCHD10-related neurodegeneration: molecular pathogenesis and the path to precision therapy. Biochemical Society transactions 19 37021679
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
2022 CHCHD10 Modulates Thermogenesis of Adipocytes by Regulating Lipolysis. Diabetes 18 35709007
2022 Structures of the Wild-Type and S59L Mutant CHCHD10 Proteins Important in Amyotrophic Lateral Sclerosis-Frontotemporal Dementia. ACS chemical neuroscience 17 35349255
2016 Genetic analysis of CHCHD10 in French familial amyotrophic lateral sclerosis patients. Neurobiology of aging 13 27095681
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 and CHCHD10: Future therapeutic targets in cognitive disorder and motor neuron disorder. Frontiers in neuroscience 12 36061599
2021 Early death of ALS-linked CHCHD10-R15L transgenic mice with central nervous system, skeletal muscle, and cardiac pathology. iScience 12 33659869
2017 CHCHD10 mutations in patients with amyotrophic lateral sclerosis in Mainland China. Neurobiology of aging 12 28318595
2022 Chchd10 is dispensable for myogenesis but critical for adipose browning. Cell regeneration (London, England) 11 35362877
2023 Disruption of Mitophagy Flux through the PARL-PINK1 Pathway by CHCHD10 Mutations or CHCHD10 Depletion. Cells 10 38132101
2019 Genetic and immunopathological analysis of CHCHD10 in Australian amyotrophic lateral sclerosis and frontotemporal dementia and transgenic TDP-43 mice. Journal of neurology, neurosurgery, and psychiatry 9 31690696
2018 Mutation analysis of CHCHD2 and CHCHD10 in Italian patients with mitochondrial myopathy. Neurobiology of aging 9 29519717
2016 CHCHD10 is not a frequent causative gene in Chinese ALS patients. Amyotrophic lateral sclerosis & frontotemporal degeneration 9 27077676
2024 High fat diet ameliorates mitochondrial cardiomyopathy in CHCHD10 mutant mice. EMBO molecular medicine 8 38724625
2022 Serum Creatine, Not Neurofilament Light, Is Elevated in CHCHD10-Linked Spinal Muscular Atrophy. Frontiers in neurology 8 35250809
2024 CHCHD10S59L/+ mouse model: Behavioral and neuropathological features of frontotemporal dementia. Neurobiology of disease 7 38583639
2017 Genetic analysis of CHCHD2 and CHCHD10 in Italian patients with Parkinson's disease. Neurobiology of aging 7 28108040
2023 Effects of the Jokela type of spinal muscular atrophy-related G66V mutation on the structural ensemble characteristics of CHCHD10. Proteins 5 36625206
2023 The identification of high-performing antibodies for Coiled-coil-helix-coiled-coil-helix domain containing protein 10 (CHCHD10) for use in Western Blot, immunoprecipitation and immunofluorescence. F1000Research 5 37767023
2023 NDV inhibited IFN-β secretion through impeding CHCHD10-mediated mitochondrial fusion to promote viral proliferation. Veterinary microbiology 5 38211361
2024 Loss of CHCHD2 Stability Coordinates with C1QBP/CHCHD2/CHCHD10 Complex Impairment to Mediate PD-Linked Mitochondrial Dysfunction. Molecular neurobiology 4 38453793
2025 Dose-dependent CHCHD10 dysregulation dictates motor neuron disease severity and alters creatine metabolism. Acta neuropathologica communications 3 40400037
2024 CHCHD10P80L knock-in zebrafish display a mild ALS-like phenotype. Experimental neurology 3 39260590
2023 Frontotemporal Dementia-Related V57E Mutation Impairs Mitochondrial Function and Alters the Structural Properties of CHCHD10. ACS chemical neuroscience 3 37194187
2023 CHCHD10 mutations induce tissue-specific mitochondrial DNA deletions with a distinct signature. Human molecular genetics 3 37815936
2025 Effects of the Amyotrophic Lateral Sclerosis-related Q108P Mutation on the Structural Ensemble Characteristics of CHCHD10. Current protein & peptide science 2 39444183
2025 Chchd10: A Novel Metabolic Sensor Modulating Adipose Tissue Homeostasis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2 39985288
2025 Combined impact of CHCHD10 p.Gly66Val and three other variants suggests oligogenic contributions to ALS. Frontiers in neurology 2 40170896
2023 The impacts of the mitochondrial myopathy-associated G58R mutation on the dynamic structural properties of CHCHD10. Journal of biomolecular structure & dynamics 2 37349880
2025 Nifuroxazide rescues the deleterious effects due to CHCHD10-associated MICOS defects in disease models. Brain : a journal of neurology 1 39478664
2025 Impacts of pathogenic mutations on the structures of the CHCHD10 monomer: An AlphaFold3 study linked to the generation of conformational ensembles. International journal of biological macromolecules 1 40490178
2025 Clinical, neuropathological, and biochemical characterization of ALS in a large CHCHD10 R15L family. medRxiv : the preprint server for health sciences 1 41040684
2025 SLP2/PHB Aggregates in ALS Mouse Models and Patients: Implications Beyond CHCHD10-Associated Motor Neuron Disease. International journal of molecular sciences 1 41303337
2025 Mutant CHCHD10 disrupts cytochrome c oxidation and activates mitochondrial retrograde signaling. EMBO molecular medicine 1 41420107
2025 A mouse model of CHCHD10 p.R15L familial ALS presents mild, age-related motor neuron degeneration without protein instability or mitochondrial dysfunction. bioRxiv : the preprint server for biology 1 41509469
2023 High fat diet ameliorates mitochondrial cardiomyopathy in CHCHD10 mutant mice. bioRxiv : the preprint server for biology 1 36865125
2026 A FEN1-EDCR dual-amplification strategy for ultrasensitive detection of CHCHD10 c.176C>T mutation. Biosensors & bioelectronics 0 41633268
2026 FDA-approved PDE4 inhibitors alleviate the dominant toxicity of ALS-FTD-associated CHCHD10S59L in Drosophila and human cells. iScience 0 41732281
2026 Clinical and biochemical characterization of amyotrophic lateral sclerosis in a CHCHD10 R15L family. Brain : a journal of neurology 0 41911331
2025 har-1/CHCHD10 mutations induce neurodegeneration and mitochondrial fragmentation in Caenorhabditis elegans. microPublication biology 0 40452868
2025 The CHCHD2-CHCHD10 protein complex is modulated by mitochondrial dysfunction and alters lipid homeostasis in the mouse brain. Cell death & disease 0 41053020
2024 Mitochondrial protein CHCHD10 inhibits NDV replication and reduces pathological changes. Veterinary microbiology 0 38244394
2024 FDA-approved PDE4 inhibitors reduce the dominant toxicity of ALS-FTD-associated CHCHD10 . bioRxiv : the preprint server for biology 0 38895204
2020 Meta-analysis of the association between CHCHD10 Pro34Ser variant and the risk of amyotrophic lateral sclerosis. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 0 32651855