Coiled-coil-helix-coiled-coil-helix domain-containing protein 10, mitochondrial · UniProt Q8WYQ3
CHCHD10 is a nuclear-encoded mitochondrial intermembrane-space protein, enriched at cristae junctions, that supports cristae architecture and oxidative phosphorylation (PMID:24934289, PMID:26666268). It is imported via Mia40-dependent disulfide-bond formation through its CHCH domain rather than a canonical N-terminal targeting signal, and the ALS variant Q108P blocks import to cause cytoplasmic mislocalization (PMID:29789341). Structurally, CHCHD10 is a constituent of the MICOS complex with mitofilin, CHCHD3 and CHCHD6, and forms heterodimers and a ~220 kDa high-molecular-weight complex with its paralog CHCHD2, which exist in vivo essentially exclusively as a finely tuned, stress-responsive HMW assembly (PMID:26666268, PMID:29121267, PMID:30084972, PMID:41053020). Functionally, CHCHD10 contributes to Complex I assembly and respiration and to cytochrome c oxidase (Complex IV) activity (PMID:29121267, PMID:20888800), with mutant work pinpointing IMS proteostasis and cytochrome c biogenesis (copper-dependent) as early bioenergetic requirements (PMID:41420107). Together with CHCHD2, CHCHD10 binds and restrains the OMA1 metallopeptidase to prevent aberrant cleavage of L-OPA1, and the two paralogs are partially functionally redundant; loss of both, or mutant aggregation, activates OMA1, triggering OPA1 processing, cristae disruption and the integrated stress response via DELE1 cleavage (PMID:32338760, PMID:35173147, PMID:35700042). CHCHD10 also stabilizes the SLP2-prohibitin and OPA1-mitofilin complexes (PMID:35656794, PMID:32369233). Disease-associated mutations act predominantly through gain of toxic function: S59L/S55L and G58R cause CHCHD10 to misfold into amyloid fibrils formed by its disordered N-terminal domain (a structure incompatible with disease mutations but tolerant of CHCHD2 differences, explaining co-aggregation), driving a proteotoxic mitochondrial integrated stress response, metabolic rewiring, and enhanced TDP-43 aggregation, while ablation of CHCHD10 does not reproduce disease pathology (PMID:30877432, PMID:35700042, PMID:35263592, PMID:35787294). Distinct haploinsufficiency mutations (R15L, G66V) reduce protein levels and impair Complex I assembly and respiration (PMID:29315381, PMID:29121267). CHCHD10 dysfunction links mitochondrial failure to motor pathology by promoting cytoplasmic TDP-43 accumulation and disrupting PINK1/PARL-dependent mitophagy (PMID:28585542, PMID:33772006, PMID:38132101). Mutations in CHCHD10 cause FTD/ALS-spectrum disease through these convergent mechanisms (PMID:28585542, PMID:30874923).
Established the first functional link between CHCHD10 and the respiratory chain, before its disease relevance was known.
Evidence siRNA knockdown with Complex IV activity assay in vitro
Resolved where CHCHD10 acts and that a disease mutation has structural consequences, localizing it to the IMS/cristae junctions and showing S59L disrupts the mitochondrial network and cristae.
Evidence Immunofluorescence, subcellular fractionation, S59L overexpression in HeLa with ultrastructural imaging
Defined CHCHD10's structural context by placing it in the MICOS complex and connecting MICOS disassembly to cristae loss, nucleoid disorganization and altered apoptosis.
Evidence Reciprocal Co-IP, patient fibroblasts, EM, apoptosis assays
Connected mitochondrial CHCHD10 function to the central ALS/FTD proteinopathy by showing loss of function and dominant-negative mutants drive cytoplasmic TDP-43 accumulation.
Evidence C. elegans complementation, mammalian cells, primary neurons, mouse brains
Characterized the CHCHD10-CHCHD2 partnership and the import pathway, showing heterodimer/HMW complex formation, CHCHD2-dependent oligomerization, and Mia40/CHCH-domain-dependent import disrupted by Q108P.
Evidence Reciprocal Co-IP, BN-PAGE, double-knockout cells, Mia40 KD/OE rescue, truncations, interactome MS
PMID:29112723 PMID:29121267 PMID:29789341 PMID:30084972
Distinguished mutation classes mechanistically, defining R15L/G66V as haploinsufficiency reducing protein and impairing Complex I, versus gain-of-toxic-function variants, and proposing a nuclear transcriptional/COX-scaffolding role.
Evidence Patient cells, zebrafish knockdown, BN-PAGE, COX co-purification, transcriptional reporters
PMID:29121267 PMID:29315381 PMID:29540477
Established gain-of-toxic-function in vivo and ordered the pathology, showing knock-in (not knockout) mice aggregate CHCHD10 with CHCHD2, induce mtISR via mTORC1, and target muscle before NMJ and motor neurons.
Evidence S55L/S59L knock-in mice with knockout comparison, omics, temporal histopathology, iPSC motor neurons
Identified the OMA1-OPA1 axis as the effector pathway, showing CHCHD2/CHCHD10 loss activates OMA1 to cleave L-OPA1, that the paralogs are partially redundant, and that TDP-43 lowers CHCHD10 to disassemble OPA1-mitofilin complexes.
Evidence Double-knockout and knock-in mice, OPA1 cleavage/OMA1 assays, Co-IP, fusion/respiration assays, FTLD-TDP brains
Extended CHCHD10 function to peripheral tissue physiology, linking its ATP-generating role to AChR clustering at the NMJ.
Evidence Muscle conditional knockout mice with ATP rescue, AChR clustering and electrophysiology
Mapped the downstream metabolic and stress consequences, showing R15L Complex I deficiency rewires one-carbon/TCA metabolism and AMPK/mTORC1 and triggers ER and mitochondrial UPR, while S59L chronically activates PINK1 with TDP-43 mitochondrial translocation.
Evidence Multi-omics in patient cells; Drosophila/HeLa with PINK1 manipulation and TDP-43 translocation inhibitor
Consolidated the mechanism, demonstrating CHCHD2/CHCHD10 directly suppress OMA1 and bind eIF2alpha to limit mtISR, stabilize the SLP2-prohibitin complex, and that OMA1 acts via DELE1 cleavage to drive the ISR essential for mutant-mouse survival.
Evidence Co-IP/OMA1 enzymatic assays, G58R and S59L knock-in mice with OMA1 ablation, DELE1 cleavage assay, omics, EM
PMID:35173147 PMID:35656794 PMID:35700042
Showed proteotoxic mtISR drives metabolic rewiring before bioenergetic failure and defined non-disease metabolic roles in adipocyte browning and lipolysis.
Evidence S55L knock-in heart metabolomics/flux with temporal staging; adipocyte-specific KO with ATGL rescue; KO cold-challenge; in vivo TDP-43 Co-IP
PMID:35263592 PMID:35362877 PMID:35709007
Demonstrated reconstituted aggregation behavior, showing S59L promotes self- and TDP-43 aggregation in isolated mitochondria/cell-free systems and that WT CHCHD10 suppresses TDP-43 aggregate growth.
Evidence Cell-free aggregation, isolated mitochondria, filter trap, AFM, transgenic mice, human brain
Linked CHCHD10 to mitophagy quality control, showing WT suppresses PARL to stabilize PINK1 and support Parkin recruitment/mitophagy, while mutants increase PARL activity, impair mitophagy and promote TDP-43 aggregation.
Evidence Co-IP CHCHD10-PARL, PARL activity and mitophagy flux assays, Parkin recruitment, in vivo and human FTD brain
Provided structural basis for aggregation, resolving CHCHD10 N-terminal amyloid fibrils by cryoEM and explaining why disease mutations destabilize the fold while CHCHD2 differences are tolerated, rationalizing co-aggregation.
Evidence CryoEM structure of N-terminal-domain amyloid fibrils (preprint)
Identified a CHCHD2-CHCHD10-C1QBP-ATG8 complex through which the paralogs promote autophagy initiation, recruit ULK1, and reduce protein aggregates.
Evidence Reciprocal Co-IP, iPSC CHCHD2-KO neurons, autophagy flux, ULK1 recruitment, in vivo aggregate reduction
Dissected the earliest pathogenic defect and uncoupled stress from bioenergetics, showing impaired copper homeostasis and cytochrome c biogenesis is rescuable by exogenous cytochrome c, while OMA1 catalytic inactivation delays cardiomyopathy without rescuing insolubility, cristae or OXPHOS defects.
Evidence S55L knock-in crossed with Oma1 E324Q mice, cytochrome c rescue, copper measurements, insoluble-proteome profiling
Characterized the native CHCHD2-CHCHD10 complex as an essentially obligate, stress-tunable HMW assembly conserved across tissues, with CHCHD2 loss sensitizing cells to mitochondrial stress.
Evidence Whole-body Chchd2 KO mouse, BN-PAGE, cross-tissue stress treatments
| 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 in HeLa cells causes fragmentation of the mitochondrial network and major ultrastructural abnormalities including loss, disorganization and dilatation of cristae. | Immunofluorescence, subcellular fractionation, overexpression in HeLa cells with mitochondrial network imaging | Brain | High | 24934289 |
| 2016 | CHCHD10 resides within the MICOS (mitochondrial contact site and cristae organizing system) complex together with mitofilin, CHCHD3, and CHCHD6; CHCHD10 mutations lead to MICOS complex disassembly, loss of mitochondrial cristae, decreased nucleoid number and disorganization, impaired mtDNA repair after oxidative stress, and inhibition of apoptosis by preventing cytochrome c release. | Co-immunoprecipitation, patient fibroblast analysis, immunofluorescence, electron microscopy, apoptosis assays | EMBO molecular medicine | High | 26666268 |
| 2018 | CHCHD10 localizes to the mitochondrial intermembrane space where it physically interacts with CHCHD2 and with p32/GC1QR; CHCHD10 and CHCHD2 have short half-lives suggesting regulatory rather than structural functions; CHCHD10 knockdown causes accumulation of excessive intramitochondrial iron but no bioenergetic defects; cells expressing S59L or R15L mutant CHCHD10 (but not WT) show impaired mitochondrial energy metabolism, supporting a gain-of-toxic-function mechanism. | Co-immunoprecipitation, mass spectrometry interactome, CHCHD10 knockdown cell lines, metabolic assays, mouse tissue expression analysis | Human molecular genetics | High | 29112723 |
| 2018 | The p.R15L CHCHD10 variant in ALS patient fibroblasts destabilizes the protein, causing defective assembly of Complex I, impaired cellular respiration, mitochondrial hyperfusion, and increased CHCHD2 levels; CHCHD10 and CHCHD2 co-immunoprecipitate quantitatively and co-migrate in a ~220 kDa high-molecular-weight complex by BN-PAGE, which is absent in patient cells. | Blue native PAGE, reciprocal co-immunoprecipitation, oxygen consumption assays, patient fibroblasts | Human molecular genetics | High | 29121267 |
| 2018 | CHCHD10 and CHCHD2 are similarly distributed throughout mitochondrial cristae and form heterodimers; CHCHD2 is preferentially stabilized by loss of mitochondrial membrane potential, and CHCHD10 oligomerization depends on CHCHD2 expression; disease-causing mutations in both proteins still readily form heterodimers. | CHCHD2/CHCHD10 double knockout cell lines, co-immunoprecipitation, immunofluorescence, mitochondrial stress treatments | Human molecular genetics | High | 30084972 |
| 2018 | CHCHD10 mitochondrial import is mediated by the CHCH domain rather than the proposed N-terminal mitochondrial targeting signal; mitochondrial import of CHCHD10 depends on Mia40, which introduces disulfide bonds into CHCH domain proteins; the ALS-associated Q108P mutation nearly completely blocks mitochondrial import, causing diffuse cytoplasmic localization; overexpression of Mia40 rescues mitochondrial import of CHCHD10 Q108P by enhancing disulfide-bond formation. | Truncation experiments, Mia40 knockdown and overexpression, subcellular fractionation, immunofluorescence | EMBO molecular medicine | High | 29789341 |
| 2018 | CHCHD10 co-purifies with cytochrome c oxidase (COX) and up-regulates COX activity by serving as a scaffolding protein required for MNRR1 (CHCHD2) phosphorylation mediated by ABL2; in the nucleus, CHCHD10 down-regulates expression of genes with oxygen-responsive elements (ORE) by interacting with and augmenting the transcriptional repressor CXXC5; disease variants G66V and P80L show faulty interactions with MNRR1 and COX, reducing respiration and increasing ROS, and abrogate transcriptional repression. | Co-purification with COX, nuclear fractionation, transcriptional reporter assays, co-immunoprecipitation with CXXC5, respiration and ROS assays | Journal of Biological Chemistry | Medium | 29540477 |
| 2019 | CHCHD10 S55L (equivalent to human S59L) knock-in mice accumulate CHCHD10 in aggregates together with paralog CHCHD2 specifically in affected tissues, leading to aberrant organelle morphology; these aggregates induce a potent mitochondrial integrated stress response (mtISR) through mTORC1 activation with elevation of stress-induced transcription factors, secretion of myokines, upregulated serine and one-carbon metabolism, and downregulation of respiratory chain enzymes; CHCHD10 ablation does not induce disease pathology or activate mtISR, establishing a gain-of-toxic-function mechanism. | Knock-in mouse model, immunofluorescence/immunohistochemistry, proteomic and transcriptomic analyses, metabolic assays, knockout comparison | Acta neuropathologica | High | 30877432 |
| 2020 | Loss of both CHCHD2 and CHCHD10 activates the OMA1 metallopeptidase, which cleaves long-form OPA1 (L-OPA1), causing disrupted mitochondrial cristae; OMA1 activation similarly occurs in affected tissues of mutant CHCHD10 knock-in mice; using OMA1 activation as a functional assay, CHCHD2 and CHCHD10 are found to be partially functionally redundant. | CHCHD2/CHCHD10 double knockout mice, knock-in mice, OPA1 cleavage assays, OMA1 activity assays, electron microscopy | Human molecular genetics | High | 32338760 |
| 2022 | In physiological conditions, CHCHD2 and CHCHD10 interact with OMA1 and suppress its enzyme activity, restraining initiation of the mitochondrial integrated stress response (mtISR) and suppressing OPA1 processing for mitochondrial fusion; during mitochondrial stress (CCCP treatment), CHCHD2 and CHCHD10 translocate to the cytosol and interact with eIF2α, attenuating mtISR overactivation by suppressing eIF2α phosphorylation. | Co-immunoprecipitation with OMA1, OMA1 enzymatic assay, subcellular fractionation under stress, eIF2α phosphorylation assays, knockdown experiments | Cell death & disease | Medium | 35173147 |
| 2022 | CHCHD10 interacts with Stomatin-Like Protein 2 (SLP2) and participates in stability of the prohibitin (PHB) complex in the inner mitochondrial membrane; the S59L mutation causes SLP2 and prohibitin to form aggregates in patient fibroblasts and in vivo in spinal motor neurons; PHB complex destabilization activates the OMA1 cascade with OPA1 processing leading to mitochondrial fragmentation and abnormal cristae morphogenesis. | Co-immunoprecipitation, patient fibroblasts, CHCHD10S59L/+ knock-in mice, immunohistochemistry, electron microscopy | Brain | Medium | 35656794 |
| 2022 | OMA1-mediated stress response is critical for survival of CHCHD10 G58R knock-in mice; mutant CHCHD10 aggregates apply toxic protein stress to the inner mitochondrial membrane; OMA1 acts both locally (causing mitochondrial fragmentation) and signals outside mitochondria by cleaving DELE1 to activate the integrated stress response (ISR); an isoform switch in terminal electron transport chain complex is also identified as part of this response. | CHCHD10 G58R knock-in mouse model, genetic ablation of OMA1, DELE1 cleavage assay, transcriptomic and proteomic analysis, electron microscopy | Journal of Clinical Investigation | High | 35700042 |
| 2017 | Loss of function of endogenous CHCHD10 impairs mitochondrial and synaptic integrity and promotes cytoplasmic TDP-43 accumulation; FTD/ALS-associated mutations R15L and S59L exhibit loss-of-function phenotypes in C. elegans genetic complementation assays and dominant negative activities in mammalian systems, causing mitochondrial/synaptic damage and cytoplasmic TDP-43 accumulation. | C. elegans genetic complementation, mammalian cell lines, primary neurons, mouse brains; loss-of-function and mutant overexpression with TDP-43 localization readouts | Nature communications | High | 28585542 |
| 2020 | CHCHD10 knockdown causes disassembly of OPA1-mitofilin complexes in brain; TDP-43 overexpression reduces CHCHD10 levels and promotes OPA1-mitofilin complex disassembly via CHCHD10, impairing mitochondrial fusion and respiration; wild-type CHCHD10 rescues TDP-43-induced OPA1-mitofilin complex disassembly and mitochondrial defects. | CHCHD10 knockdown, TDP-43 overexpression, co-immunoprecipitation of OPA1-mitofilin complexes, mitochondrial fusion assays, respiration assays, transgenic mice, FTLD-TDP patient brains | FASEB journal | Medium | 32369233 |
| 2020 | CHCHD10 is required for ATP production in skeletal muscle, which in turn facilitates acetylcholine receptor (AChR) expression and promotes agrin-induced AChR clustering at neuromuscular junctions; ATP addition rescues the reduction of AChR clusters in CHCHD10-ablated muscles. | Muscle conditional knockout mice, ATP rescue experiment, AChR clustering assay, electrophysiology | Human molecular genetics | Medium | 31261376 |
| 2021 | The CHCHD10 R15L variant causes a complex I deficiency that increases the NADH/NAD+ ratio, diminishes TCA cycle activity, reorganizes one-carbon metabolism, raises AMP/ATP ratio leading to AMPK phosphorylation and mTORC1 inhibition; these metabolic changes activate the UPR in the ER through IRE1/XBP1 and the mitochondrial UPR via ATF4/ATF5 upregulation. | Multi-omics (transcriptomics, metabolomics, proteomics) in patient cells under energetic stress | Human molecular genetics | Medium | 33749723 |
| 2021 | CHCHD10 S59L mutation in Drosophila and HeLa cells increases TDP-43 insolubility and mitochondrial translocation; blocking TDP-43 mitochondrial translocation with a peptide inhibitor reduces CHCHD10 S59L-mediated toxicity; CHCHD10 S59L also chronically activates the PINK1 pathway, and genetic/pharmacological modulation of PINK1 rescues CHCHD10 S59L-induced phenotypes. | Drosophila model, HeLa cell model, peptide inhibitor of TDP-43 translocation, PINK1 genetic and pharmacological manipulation | Nature communications | High | 33772006 |
| 2023 | CHCHD10 mutations (R15L and S59L) reduce PINK1 levels by increasing PARL protease activity, whereas wild-type CHCHD10 suppresses PARL activity through direct interaction, thereby promoting PINK1 stability and mitophagy flux; CHCHD10 mutations impair mitochondrial Parkin recruitment and mitophagy flux, and impaired mitophagy promotes TDP-43 aggregation. | In vivo and in vitro models, PARL activity assays, co-immunoprecipitation of CHCHD10-PARL, mitophagy flux assays, Parkin recruitment assays, human FTD brain tissue | Cells | Medium | 38132101 |
| 2010 | CHCHD10 plays a role in complex IV (cytochrome c oxidase) activity, confirmed by gene knockdown in vitro. | siRNA knockdown, complex IV activity assay | Biochemical and biophysical research communications | Medium | 20888800 |
| 2018 | The p.R15L and p.G66V CHCHD10 mutations cause haploinsufficiency: CHCHD10 protein levels are reduced to ~50% in patient cells (p.R15L at the mRNA level; p.G66V through altered secondary structure and rapid protein degradation); knockdown of CHCHD10 in zebrafish to ~50% causes motoneuron pathology, abnormal myofibrillar structure and motility deficits in vivo. | Patient fibroblast protein/mRNA quantification, secondary structure analysis, zebrafish knockdown model with behavioral and histological readouts | Human molecular genetics | Medium | 29315381 |
| 2019 | CHCHD10 S59L/+ knock-in mice develop OXPHOS deficiency in muscle at 3 months, prior to neuromuscular junction fragmentation and motor neuron loss, establishing that the pathological effects of the mutation target muscle before NMJ and motor neurons; CHCHD10 is highly expressed at the NMJ postsynaptic part and S59L mutation causes abnormal CHCHD10 expression at motor end plates. | CHCHD10 S59L/+ knock-in mice, temporal histopathological analysis, OXPHOS enzyme histochemistry, motor neuron counting, NMJ morphology assessment, iPSC-derived motor neurons | Acta neuropathologica | High | 30874923 |
| 2019 | CHCHD2 T61I mutation causes increased interaction with CHCHD10 and reduced CHCHD10 protein levels; mitochondrial ultrastructural alterations in CHCHD2 T61I patient fibroblasts are similar to those caused by CHCHD10 mutations, implicating CHCHD10 in CHCHD2-related Parkinson's disease pathogenesis. | Co-immunoprecipitation in patient fibroblasts, Western blot quantification, electron microscopy | Neurobiology of aging | Medium | 30530185 |
| 2022 | CHCHD10 deficiency leads to disorganization of mitochondrial cristae, impairment of OXPHOS complex assembly, inhibition of ATP generation, and downregulation of lipolysis through reduced ATGL protein synthesis; augmented lipolysis by ATGL overexpression restores thermogenesis in adipocyte-specific Chchd10 knockout mice. | Adipocyte-specific conditional knockout mice, ATGL overexpression rescue, OXPHOS complex assembly assay, ATP measurement, lipolysis assay | Diabetes | Medium | 35709007 |
| 2022 | During myogenesis, CHCHD10 interacts with TDP-43 in regenerating myofibers and newly differentiated myotubes; Chchd10 knockout mice have normal skeletal muscle development but blunted cold-induced browning of white adipose tissue with markedly reduced UCP1, indicating CHCHD10 is required for cold-induced, mitochondrion-dependent browning. | Co-immunoprecipitation in vivo and ex vivo, Chchd10 knockout mice, cold challenge assay, UCP1 Western blot | Cell regeneration | Medium | 35362877 |
| 2022 | CHCHD10 S59L mutant knock-in mouse hearts show an extensive metabolic rewiring triggered by proteotoxic mtISR before bioenergetic impairment onset: a switch from oxidative to glycolytic metabolism, enhancement of transsulfuration and one-carbon metabolism, and increased NADPH oxidases activating antioxidant responses with heme depletion. | CHCHD10 S55L knock-in mouse model, metabolomics, transcriptomics, metabolic flux analysis, temporal disease staging | Cell reports | High | 35263592 |
| 2022 | CHCHD10 S59L mutation induces aggregation of resident CHCHD10 protein in isolated mitochondria and simultaneously enhances aggregation of recombinant TDP-43 imported into mitochondria; wild-type CHCHD10 inhibits the growth of TDP-43 aggregates in an in vitro cell-free system, as demonstrated by filter trap assay and atomic force microscopy. | In vitro cell-free aggregation assay, isolated mitochondria, filter trap assay, atomic force microscopy, transgenic mice, human brain tissue | Acta neuropathologica communications | Medium | 35787294 |
| 2024 | CHCHD10 amyloid fibrils formed by the disordered N-terminal domain of CHCHD10 have a cryoEM-resolved structure; disease-associated mutations cannot be accommodated by the WT fibril structure, whereas sequence differences between CHCHD10 and CHCHD2 are tolerated, explaining co-aggregation of the two proteins. | CryoEM structure determination of amyloid fibrils formed by N-terminal domain of CHCHD10 | bioRxivpreprint | High | |
| 2025 | Mutant CHCHD10 S55L causes impaired mitochondrial copper homeostasis and defective cytochrome c oxidation as an early bioenergetic defect; defective respiration in mutant mitochondria is rescued by exogenous addition of cytochrome c, pinpointing IMS proteostasis disruption affecting cytochrome c biogenesis as a key pathogenic mechanism; OMA1 catalytic inactivation in Chchd10 S55L/+ mice delays cardiomyopathy onset without rescuing CHCHD10 insolubility, cristae defects or OXPHOS impairment, demonstrating mtISR can be uncoupled from bioenergetic collapse. | CHCHD10 S55L knock-in mice crossed with Oma1 E324Q knock-in mice, cytochrome c rescue assay, copper homeostasis measurements, proteomic profiling of insoluble mitochondrial proteins | EMBO molecular medicine | High | 41420107 |
| 2024 | CHCHD2 and CHCHD10 interact with ATG8-family proteins (preferentially GABARAPs) and with C1QBP/p32 to form a CHCHD2-CHCHD10-C1QBP-ATG8 complex; through GABARAP binding, CHCHD2 and CHCHD10 undergo autophagic degradation and recruit the ULK1 complex; CHCHD2 and CHCHD10 promote autophagy initiation and reduce protein aggregates. | Co-immunoprecipitation, iPSC-derived CHCHD2 knockout neurons, autophagy flux assays, ULK1 complex recruitment assay, in vivo α-synuclein aggregate reduction | Autophagy | Medium | 42183628 |
| 2025 | In mouse tissues, CHCHD2 and CHCHD10 exist exclusively as a high molecular weight complex whose levels are finely tuned; in response to mitochondrial dysfunction, the abundance and size of the CHCHD2-CHCHD10 complex increase, a mechanism conserved across different tissues; loss of CHCHD2 does not abolish CHCHD10 oligomerization but enhances cell vulnerability to mitochondrial stress. | Whole-body Chchd2 knockout mouse, BN-PAGE complex analysis, mitochondrial stress treatments across tissues | Cell death & disease | Medium | 41053020 |
| 2025 | Nifuroxazide rescues mitochondrial network fragmentation and cristae abnormalities in CHCHD10 S59L/+ patient fibroblasts; the rescue mechanism involves KIF5B-mediated mitochondrial transport enhancement with increased axonal movement and syntaphilin degradation in patient-derived motor neurons. | Drug screen in yeast MICOS mutant strains, patient fibroblast rescue assay, iPSC-derived motor neuron live imaging, syntaphilin quantification | Brain | Medium | 39478664 |
| Year | Title | Journal | Citations | PMID |
|---|---|---|---|---|
| 2014 | A mitochondrial origin for frontotemporal dementia and amyotrophic lateral sclerosis through CHCHD10 involvement. | Brain : a journal of neurology | 408 | 24934289 |
| 2016 | CHCHD10 mutations promote loss of mitochondrial cristae junctions with impaired mitochondrial genome maintenance and inhibition of apoptosis. | EMBO molecular medicine | 160 | 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 |
| 2017 | Loss of function CHCHD10 mutations in cytoplasmic TDP-43 accumulation and synaptic integrity. | Nature communications | 100 | 28585542 |
| 2014 | Mutation in the novel nuclear-encoded mitochondrial protein CHCHD10 in a family with autosomal dominant mitochondrial myopathy. | Neurogenetics | 100 | 25193783 |
| 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 | 89 | 29112723 |
| 2019 | ALS/FTD mutant CHCHD10 mice reveal a tissue-specific toxic gain-of-function and mitochondrial stress response. | Acta neuropathologica | 88 | 30877432 |
| 2019 | Mitochondrial defect in muscle precedes neuromuscular junction degeneration and motor neuron death in CHCHD10S59L/+ mouse. | Acta neuropathologica | 79 | 30874923 |
| 2015 | CHCHD10 variant p.(Gly66Val) causes axonal Charcot-Marie-Tooth disease. | Neurology. Genetics | 72 | 27066538 |
| 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 |
| 2016 | Investigating the role of ALS genes CHCHD10 and TUBA4A in Belgian FTD-ALS spectrum patients. | Neurobiology of aging | 60 | 28069311 |
| 2019 | PD-linked CHCHD2 mutations impair CHCHD10 and MICOS complex leading to mitochondria dysfunction. | Human molecular genetics | 58 | 30496485 |
| 2022 | OMA1 mediates local and global stress responses against protein misfolding in CHCHD10 mitochondrial myopathy. | The Journal of clinical investigation | 57 | 35700042 |
| 2018 | The cellular stress proteins CHCHD10 and MNRR1 (CHCHD2): Partners in mitochondrial and nuclear function and dysfunction. | The Journal of biological chemistry | 57 | 29540477 |
| 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 | 54 | 33749723 |
| 2018 | CHCHD2 accumulates in distressed mitochondria and facilitates oligomerization of CHCHD10. | Human molecular genetics | 54 | 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 | 54 | 30092269 |
| 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 |
| 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 | 37 | 31261376 |
| 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 | 36 | 32369233 |
| 2010 | Functional annotation of heart enriched mitochondrial genes GBAS and CHCHD10 through guilt by association. | Biochemical and biophysical research communications | 36 | 20888800 |
| 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 | 26 | 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 |
| 2022 | Modulation of synaptic plasticity, motor unit physiology, and TDP-43 pathology by CHCHD10. | Acta neuropathologica communications | 24 | 35787294 |
| 2019 | Mitochondrial CHCHD2 and CHCHD10: Roles in Neurological Diseases and Therapeutic Implications. | The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry | 24 | 31526091 |
| 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 |
| 2022 | CHCHD10 Modulates Thermogenesis of Adipocytes by Regulating Lipolysis. | Diabetes | 20 | 35709007 |
| 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 | Structures of the Wild-Type and S59L Mutant CHCHD10 Proteins Important in Amyotrophic Lateral Sclerosis-Frontotemporal Dementia. | ACS chemical neuroscience | 18 | 35349255 |
| 2022 | CHCHD2 and CHCHD10: Future therapeutic targets in cognitive disorder and motor neuron disorder. | Frontiers in neuroscience | 13 | 36061599 |
| 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 |
| 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 |
| 2024 | High fat diet ameliorates mitochondrial cardiomyopathy in CHCHD10 mutant mice. | EMBO molecular medicine | 9 | 38724625 |
| 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 | CHCHD10S59L/+ mouse model: Behavioral and neuropathological features of frontotemporal dementia. | Neurobiology of disease | 8 | 38583639 |
| 2022 | Serum Creatine, Not Neurofilament Light, Is Elevated in CHCHD10-Linked Spinal Muscular Atrophy. | Frontiers in neurology | 8 | 35250809 |
| 2017 | Genetic analysis of CHCHD2 and CHCHD10 in Italian patients with Parkinson's disease. | Neurobiology of aging | 7 | 28108040 |
| 2025 | Dose-dependent CHCHD10 dysregulation dictates motor neuron disease severity and alters creatine metabolism. | Acta neuropathologica communications | 5 | 40400037 |
| 2024 | Loss of CHCHD2 Stability Coordinates with C1QBP/CHCHD2/CHCHD10 Complex Impairment to Mediate PD-Linked Mitochondrial Dysfunction. | Molecular neurobiology | 5 | 38453793 |
| 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 |
| 2023 | CHCHD10 mutations induce tissue-specific mitochondrial DNA deletions with a distinct signature. | Human molecular genetics | 4 | 37815936 |
| 2025 | Chchd10: A Novel Metabolic Sensor Modulating Adipose Tissue Homeostasis. | Advanced science (Weinheim, Baden-Wurttemberg, Germany) | 3 | 39985288 |
| 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 |
| 2025 | Effects of the Amyotrophic Lateral Sclerosis-related Q108P Mutation on the Structural Ensemble Characteristics of CHCHD10. | Current protein & peptide science | 2 | 39444183 |
| 2025 | Combined impact of CHCHD10 p.Gly66Val and three other variants suggests oligogenic contributions to ALS. | Frontiers in neurology | 2 | 40170896 |
| 2025 | Mutant CHCHD10 disrupts cytochrome c oxidation and activates mitochondrial retrograde signaling. | EMBO molecular medicine | 2 | 41420107 |
| 2023 | High fat diet ameliorates mitochondrial cardiomyopathy in CHCHD10 mutant mice. | bioRxiv : the preprint server for biology | 2 | 36865125 |
| 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 | The CHCHD2-CHCHD10 protein complex is modulated by mitochondrial dysfunction and alters lipid homeostasis in the mouse brain. | Cell death & disease | 1 | 41053020 |
| 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 | 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 |
| 2024 | Mitochondrial protein CHCHD10 inhibits NDV replication and reduces pathological changes. | Veterinary microbiology | 1 | 38244394 |
| 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 |
| 2026 | CHCHD2 and CHCHD10 promoted autophagic clearance of protein aggregates via GABARAPs. | Autophagy | 0 | 42183628 |
| 2025 | har-1/CHCHD10 mutations induce neurodegeneration and mitochondrial fragmentation in Caenorhabditis elegans. | microPublication biology | 0 | 40452868 |
| 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 |
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