Affinage

ATAD3A

ATPase family AAA domain-containing protein 3A · UniProt Q9NVI7

Length
586 aa
Mass
66.2 kDa
Annotated
2026-04-28
58 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATAD3A is a mitochondrial inner membrane AAA+ ATPase that spans both mitochondrial membranes—with its N-terminus facing the intermembrane space/cytoplasm and its C-terminal ATPase domain in the matrix—and functions as a central scaffold coupling mitochondrial membrane architecture, nucleoid dynamics, mitophagy regulation, and ER–mitochondria communication (PMID:20154147, PMID:20349121). Its ATPase domain directly binds TFAM to drive ATP-dependent nucleoid trafficking along mitochondria, while its oligomerization state—modulated by SIRT3-dependent acetylation at K134, TBK1 phosphorylation at S321, and interaction with Drp1 and sigma-1 receptor—controls mitochondrial fission/fusion balance and mtDNA maintenance (PMID:36383603, PMID:30914652, PMID:38250153, PMID:39520088, PMID:36736924). ATAD3A bridges the TOM40/TIM23 import machinery to facilitate PINK1 import and processing, thereby suppressing PINK1/Parkin-dependent mitophagy; its own stability is regulated by opposing ubiquitination by TRIM25 (K48-linked, destabilizing) and FBXL6 (K63-linked, stabilizing) (PMID:29242539, PMID:39307194, PMID:40975350). At mitochondria-associated ER membranes, ATAD3A interacts with PERK to shield local translation from ER stress-induced repression, associates with the IP3R1–GRP75–VDAC1 complex to regulate calcium homeostasis, and interacts with NDUFS8 to support respiratory complex I assembly (PMID:39116259, PMID:38250153, PMID:40961994).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2010 High

    Establishing the dual-membrane topology and scaffolding function of ATAD3A resolved how a single AAA+ ATPase could coordinate outer and inner mitochondrial membrane dynamics and cholesterol channeling.

    Evidence Dominant-negative mutagenesis, Drosophila invalidation, subcellular fractionation, and back-titration ELISA/immunofluorescence on purified human mitochondria

    PMID:20154147 PMID:20349121

    Open questions at the time
    • Mechanism by which ATAD3A mediates cholesterol transfer at contact sites is undefined
    • No structural model of the dual-membrane spanning architecture
  2. 2010 High

    Identification of S100B as a cytoplasmic chaperone for newly synthesized ATAD3A revealed a quality-control step that prevents ATAD3A aggregation prior to mitochondrial import.

    Evidence NMR mapping of S100B-binding motif on ATAD3A, Co-IP, and cellular localization assays in oligodendrocyte progenitors

    PMID:20351179

    Open questions at the time
    • Whether S100B is the sole cytoplasmic chaperone for ATAD3A is untested
    • Relevance of this interaction outside oligodendrocyte lineage cells is unknown
  3. 2012 Medium

    Discovery that paralog ATAD3B hetero-oligomerizes with ATAD3A and acts as its dominant-negative regulator established that nucleoid interaction and mitochondrial morphology are tuned by the ATAD3A/ATAD3B ratio.

    Evidence Gain- and loss-of-function of ATAD3B, Co-IP with ATAD3A, morphology analysis

    PMID:22664726

    Open questions at the time
    • Stoichiometry and structural basis of ATAD3A–ATAD3B hetero-oligomers are undefined
    • Single-lab finding not independently replicated
  4. 2017 High

    Linking ATAD3A to the TOM40/TIM23 import machinery and showing that its loss triggers PINK1 accumulation and hyperactive mitophagy established ATAD3A as a gatekeeper of PINK1-dependent mitophagy.

    Evidence Co-IP of ATAD3A with TOM40/TIM23, conditional Atad3a KO mouse, genetic rescue by Pink1 deletion

    PMID:29242539

    Open questions at the time
    • Whether ATAD3A directly chaperones PINK1 through the import channel or acts indirectly is unresolved
    • Relative contributions of ATAD3A versus other import factors to PINK1 processing are unclear
  5. 2017 High

    Demonstrating that a Walker A mutant (G355D) abolishes ATPase activity and fragments mitochondria provided the first direct evidence that catalytic cycling is required for ATAD3A's structural and signaling roles.

    Evidence In vitro ATPase assay on recombinant mutant, patient fibroblast and iPSC-neuron analysis

    PMID:28158749

    Open questions at the time
    • No high-resolution structure of the ATPase domain to explain how the mutation disrupts cycling
    • Whether residual monomeric ATAD3A retains non-catalytic functions is untested
  6. 2019 High

    Revealing that ATAD3A dimerization is driven by deacetylation at K135, recruits Drp1, and disrupts TFAM/mtDNA binding unified the previously separate observations on mitochondrial dynamics and nucleoid maintenance under a single oligomerization-dependent mechanism.

    Evidence Co-IP of Drp1/ATAD3A, K135 mutagenesis, TFAM/mtDNA ChIP, DA1 peptide rescue in HD transgenic mice

    PMID:30914652

    Open questions at the time
    • Structural basis for how oligomerization state switches TFAM binding versus Drp1 interaction is unknown
    • Whether DA1 peptide has off-target effects beyond blocking Drp1–ATAD3A interaction
  7. 2021 High

    Showing that ATAD3A deficiency triggers mtDNA-dependent cGAS-STING activation and type I interferon signaling established a direct link between ATAD3A's nucleoid-organizing role and innate immune surveillance.

    Evidence siRNA knockdown in THP-1, mtDNA depletion rescue, ISG expression and IFNα ELISA

    PMID:34387651

    Open questions at the time
    • Route by which mtDNA escapes mitochondria upon ATAD3A loss (herniation vs. mPTP vs. BAX/BAK pores) is undefined
    • Whether interferon activation is direct or secondary to mitophagy defects is unresolved
  8. 2021 High

    Identification of ATAD3A as a scaffolding protein regularly distributed along the inner membrane and associated with complex I, Letm1, and prohibitin complexes—with neuronal KO causing cristae disorganization—established it as a general inner membrane organizer beyond its nucleoid and mitophagy roles.

    Evidence Proteomics, Co-IP, STORM super-resolution imaging, neuronal conditional KO mouse

    PMID:34936866

    Open questions at the time
    • Whether ATAD3A directly shapes cristae or acts indirectly through MICOS/prohibitin interactions is unknown
    • Stoichiometry with inner membrane partners is not determined
  9. 2022 High

    Demonstrating that ATAD3A's ATPase domain directly binds TFAM and that oligomerization via the coiled-coil domain drives ATP-dependent nucleoid trafficking provided the first mechanistic model for active nucleoid movement along the inner membrane.

    Evidence Live imaging of nucleoid dynamics, direct binding assay ATAD3A-TFAM, coiled-coil mutagenesis

    PMID:36383603

    Open questions at the time
    • Motor-like versus treadmilling mechanism for nucleoid movement is unresolved
    • Whether ATAD3A moves along a track or remodels the membrane to translocate nucleoids
  10. 2022 High

    Linking ATAD3A oligomerization at MAMs to suppression of CYP46A1 and cholesterol accumulation in Alzheimer's disease models extended the pathological consequences of aberrant oligomerization from mitochondrial dynamics to lipid metabolism and neurodegeneration.

    Evidence 5XFAD AD mouse, heterozygous ATAD3A KO, DA1 peptide, CYP46A1 expression, cholesterol assays

    PMID:35236834

    Open questions at the time
    • Mechanism by which ATAD3A oligomers at MAMs suppress CYP46A1 gene expression is unclear
    • Whether cholesterol accumulation is primary or secondary to mitochondrial/MAM disruption
  11. 2024 High

    Discovery that ATAD3A at MAMs competes with eIF2α for PERK binding to protect local mitochondrial translation from ER stress–induced repression revealed a subcellular compartmentalization of the integrated stress response mediated by ATAD3A.

    Evidence Live-cell translation reporter imaging, Co-IP of PERK/ATAD3A/eIF2, proximity ligation assay, ATAD3A knockdown

    PMID:39116259

    Open questions at the time
    • Whether this mechanism extends to all MAM-localized mRNAs or a specific subset
    • Structural basis for the competitive PERK-binding mechanism
  12. 2024 Medium

    Identification of SIRT3-mediated deacetylation at K134 as a switch controlling ATAD3A oligomerization and its interaction with the IP3R1–GRP75–VDAC1 calcium-transfer complex at MAMs linked ATAD3A's oligomeric state to mitochondrial calcium homeostasis and cardiac hypertrophy.

    Evidence SIRT3 KO mouse, K134 site-directed mutagenesis, Co-IP, calcium imaging, MAM analysis, cardiac hypertrophy model

    PMID:38250153

    Open questions at the time
    • Single-lab finding not independently confirmed
    • Whether K134 and K135 acetylation events are redundant or sequential is undetermined
    • Direct acetylation by a specific acetyltransferase is not identified
  13. 2024 High

    Demonstrating that TBK1 phosphorylates ATAD3A at S321 to enhance PINK1 import and suppress mitophagy during senescence identified the first kinase directly modifying ATAD3A and connected innate immune kinase signaling to mitophagy regulation.

    Evidence In vitro kinase assay, S321A mutagenesis, TAT-PEP blocking peptide, senescence assays, aging mouse models

    PMID:39520088

    Open questions at the time
    • Whether phosphatases reverse S321 phosphorylation to re-enable mitophagy is unknown
    • Crosstalk between S321 phosphorylation and K134/K135 acetylation is unexplored
  14. 2024 Medium

    Defining opposing ubiquitination modes—TRIM25-mediated K48-linked degradation versus FBXL6-mediated K63-linked stabilization—established that ATAD3A protein levels are under bidirectional ubiquitin code control, with downstream effects on PINK1/Parkin mitophagy and metabolic reprogramming.

    Evidence Co-IP, ubiquitination assays with chain-type specificity, proteasome inhibitor experiments, in vivo tumor and ischemia models

    PMID:39307194 PMID:40975350

    Open questions at the time
    • Each ubiquitin ligase studied by a different single lab; no integrated study of both pathways
    • Lysine residues on ATAD3A targeted by each E3 ligase are not mapped
    • Whether deubiquitinases regulate ATAD3A turnover is unknown
  15. 2025 Medium

    Demonstrating that ATAD3A interacts with complex I subunit NDUFS8 and is required for complex I assembly and activity resolved how ATAD3A contributes to respiratory chain function and linked its deficiency to reverse electron transport and mitochondrial ROS production.

    Evidence Co-IP of ATAD3A/NDUFS8, complex I activity assay, ROS and membrane potential measurements in C. elegans and mammalian cells

    PMID:40961994

    Open questions at the time
    • Single-lab finding; independent replication needed
    • Whether ATAD3A is a bona fide assembly factor or stabilizes mature complex I is unresolved
    • No structural information on ATAD3A–NDUFS8 interface

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structural model of ATAD3A in its native dual-membrane context is lacking, and the precise mechanism by which its oligomerization state switches between scaffolding, nucleoid trafficking, mitophagy regulation, and pore formation remains to be dissected at the molecular level.
  • No cryo-EM or crystal structure of full-length ATAD3A or its oligomeric assemblies
  • Hierarchy and crosstalk among post-translational modifications (acetylation, phosphorylation, ubiquitination) in regulating oligomeric state are uncharacterized
  • Whether ATAD3A constitutes the pore-forming subunit of the mPTP awaits peer-reviewed confirmation and independent replication

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 4 GO:0005198 structural molecule activity 2 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005739 mitochondrion 4 GO:0005783 endoplasmic reticulum 3
Pathway
R-HSA-9612973 Autophagy 6 R-HSA-1852241 Organelle biogenesis and maintenance 4 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-1430728 Metabolism 1 R-HSA-168256 Immune System 1
Partners
DRP1NDUFS8PERKPINK1TFAMTIM23TOM40VDAC1
Complex memberships
IP3R1-GRP75-VDAC1 MAM calcium complexTOM40/TIM23 import complex (bridging interaction)

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 ATAD3A spans both mitochondrial membranes: its N-terminal domain interacts with the outer membrane, a central transmembrane segment anchors it in the inner membrane, and the C-terminal AAA+ ATPase domain is positioned in the matrix. Using dominant-negative mutants (defective ATP-binding and truncated N-terminus), ATAD3A was shown to regulate dynamic interactions between the outer and inner mitochondrial membranes, and is required for normal cell growth and cholesterol channeling at contact sites. Dominant-negative mutagenesis, Drosophila invalidation, human steroidogenic cell knockdown, subcellular fractionation Molecular and cellular biology High 20154147
2010 ATAD3A topology was directly determined: the N-terminal region (aa 40-53) is accessible from outside the inner membrane (cytoplasm or intermembrane space) and the C-terminal region (aa 572-586) is located within the matrix, confirmed by back-titration ELISA and immunofluorescence using domain-specific antibodies on purified human mitochondria. Anti-peptide antibody back-titration ELISA, immunofluorescence on purified human mitochondria Journal of bioenergetics and biomembranes High 20349121
2010 ATAD3A is a major, high-affinity, calcium-dependent binding target of S100B in oligodendrocyte progenitor cells. NMR spectroscopy defined a consensus calcium-dependent S100B binding motif on ATAD3A. S100B prevents cytoplasmic ATAD3A aggregation and restores its mitochondrial localization, suggesting S100B assists newly synthesized ATAD3A in proper folding and subcellular targeting. Co-immunoprecipitation, NMR spectroscopy, cellular truncation mutant studies, Far-Western assay Molecular and cellular biology High 20351179
2012 ATAD3B, a paralog of ATAD3A, associates with ATAD3A and acts as a dominant negative regulator: it negatively regulates ATAD3A interaction with matrix nucleoid complexes and promotes mitochondrial fragmentation. Loss- and gain-of-function, co-immunoprecipitation, mitochondrial morphology analysis Mitochondrion Medium 22664726
2015 ATAD3A interacts with the metastasis-promoting protein WASF3 at the mitochondrial membrane (N-terminal WASF3 interacts with N-terminal ATAD3A), and also forms a complex with GRP78. ATAD3A-mediated stabilization of WASF3 occurs through this interaction with GRP78, bridging ER and mitochondria. Knockdown of ATAD3A reduces WASF3 protein levels and suppresses invasion and metastasis. Mass spectrometry, co-immunoprecipitation, proteolysis of isolated mitochondria, siRNA knockdown, in vivo xenograft Oncogene High 25823022
2016 A recurrent de novo ATAD3A p.Arg528Trp variant acts through a dominant-negative mechanism, causing small mitochondria that trigger mitophagy and reduction in mitochondrial content. Tissue-specific overexpression of the homologous Drosophila mutation decreases mitochondrial content and causes aberrant morphology; patient fibroblasts show increased mitophagy. Drosophila tissue-specific overexpression, patient fibroblast mitophagy assay, whole-exome sequencing American journal of human genetics High 27640307
2017 ATAD3A interacts with mitochondrial channel components TOM40 and TIM23 and serves as a bridging factor to facilitate appropriate transport and processing of PINK1. Loss of ATAD3A causes PINK1 accumulation and hyperactivation of PINK1-dependent mitophagy, which can be rescued by deletion of Pink1. Co-immunoprecipitation, conditional knockout mouse, genetic epistasis (Atad3a/Pink1 double KO), flow cytometry, bone marrow analysis Nature immunology High 29242539
2017 A dominant-negative ATAD3A mutation (p.G355D) affecting the Walker A motif (responsible for ATP binding) causes markedly reduced ATPase activity in the recombinant mutant protein and fragments the mitochondrial network, induces lysosome mass, and upregulates basal autophagy through mTOR inactivation in patient fibroblasts and iPSC-derived neurons. In vitro ATPase activity assay on recombinant mutant protein, patient fibroblast and iPSC-derived neuron analysis, mitochondrial morphology imaging, mTOR pathway western blot Human molecular genetics High 28158749
2019 In Huntington's disease, ATAD3A dimerization (driven by deacetylation at K135) is required for Drp1-mediated mitochondrial fragmentation. ATAD3A interacts with Drp1 in HD cells. ATAD3A oligomerization disrupts TFAM/mtDNA binding, impairing mtDNA maintenance. A blocking peptide (DA1) targeting the Drp1/ATAD3A interaction abolishes ATAD3A oligomerization, restores mtDNA maintenance, and reduces HD neurodegeneration in transgenic mice. Proteomic analysis, co-immunoprecipitation (Drp1/ATAD3A), mutagenesis (K135), TFAM/mtDNA ChIP, peptide inhibition (DA1), HD transgenic mouse behavioral/neuropathological analysis Nature communications High 30914652
2021 Knockdown of ATAD3A in THP-1 cells increases interferon signaling mediated by cGAS and STING. This enhanced interferon signaling is abrogated when cells are depleted of mitochondrial DNA, establishing that ATAD3A mutations lead to mtDNA-driven cGAS-STING activation and a type I interferonopathy. siRNA knockdown in THP-1 cells, mtDNA depletion, ISG expression measurement, interferon-alpha ELISA The Journal of experimental medicine High 34387651
2021 AMBRA1, upon mitochondrial depolarization, is recruited to the outer mitochondrial membrane and interacts with both PINK1 and ATAD3A. AMBRA1 promotes PINK1 stability by preventing its enhanced degradation by the mitochondrial protease LONP1; ATAD3A silencing rescues defective PINK1 accumulation in AMBRA1-deficient cells. Co-immunoprecipitation (AMBRA1/PINK1/ATAD3A), siRNA knockdown, LONP1 protease assay, ubiquitin phosphorylation assay, PARKIN recruitment assay Autophagy High 34798798
2021 ATAD3A associates with different inner mitochondrial membrane components including OXPHOS complex I, Letm1, and prohibitin complexes. STORM microscopy shows ATAD3A is regularly distributed along the inner mitochondrial membrane. Neuronal conditional knockout mice develop severe encephalopathy with aberrant mitochondrial cristae morphogenesis, supporting a primary scaffolding role for ATAD3A in inner mitochondrial membrane organization. Multi-omics (proteomics), co-immunoprecipitation, STORM super-resolution microscopy, neuronal conditional knockout mouse Cell reports High 34936866
2022 ATAD3A oligomerization in Alzheimer's disease models accumulates at mitochondria-associated ER membranes (MAMs) and inhibits gene expression of CYP46A1, an enzyme governing brain cholesterol clearance, leading to cholesterol accumulation. Suppression of ATAD3A oligomerization by heterozygous KO or DA1 peptide restores CYP46A1 levels, normalizes cholesterol turnover and MAM integrity, and reduces AD neuropathology. 5XFAD mouse model, heterozygous ATAD3A KO, peptide inhibition (DA1), CYP46A1 gene expression analysis, cholesterol assay, MAM fractionation, behavioral testing Nature communications High 35236834
2022 ATAD3A's ATPase domain binds directly to TFAM and mediates nucleoid trafficking along mitochondria by ATP hydrolysis. Nucleoid trafficking also requires ATAD3A oligomerization via coiled-coil domain interactions in the intermembrane space. In ATAD3A deficiency, nucleoid trafficking is impaired, leading to dispersed small nucleoids and enhanced respiratory complex formation. Live imaging of nucleoid dynamics, ATPase domain-TFAM direct binding assay, coiled-coil domain mutagenesis, ATAD3A-deficient cells, respiratory complex analysis Proceedings of the National Academy of Sciences of the United States of America High 36383603
2022 ATAD3A interacts with ERK1/2 in the mitochondria in the presence of VDAC1, and this interaction is essential for activation of mitochondrial ERK1/2 signaling in a RAS-independent manner. A Walker A dead mutant (K358) of ATAD3A acts as a dominant negative, demonstrating that ATPase activity is required for this signaling function. Co-immunoprecipitation (ATAD3A/ERK1/2/VDAC1), CRISPR/Cas9 knockout, dominant-negative mutagenesis, phospho-kinase profiling, orthotopic xenograft mouse Journal of experimental & clinical cancer research Medium 35093151
2022 MUC1 translocates to mitochondria and interacts with ATAD3A, inducing its degradation. This relieves ATAD3A-mediated cleavage of PINK1, leading to PINK1 accumulation and increased mitophagy to promote cancer cell malignancy. Co-immunoprecipitation (MUC1/ATAD3A), western blot for PINK1 levels, mitophagy assay, in vivo xenograft Cell death & disease Medium 36289190
2023 PINK1 is recruited to mitochondria for degradation via mitophagy upon ATAD3A-mediated regulation. The ATAD3A-PINK1 axis controls PD-L1 subcellular distribution: PINK1 recruits PD-L1 to mitochondria for degradation, while ATAD3A restrains this process. Paclitaxel increases ATAD3A expression to disrupt PD-L1 proteostasis by restraining PINK1-dependent mitophagy. Co-immunoprecipitation, subcellular fractionation, mitophagy assays, patient tumor sample analysis, preclinical mouse models Cell research Medium 36627348
2023 Sigma-1 receptor (σ1R) at the MAM interacts with ATAD3A and retains it as a monomer, thereby inhibiting ATAD3A dimerization and mitochondrial fragmentation. In σ1R-deficient or SOD1-ALS mouse spinal cords, ATAD3A dimerization and mitochondrial fragmentation are induced. Co-immunoprecipitation (σ1R/ATAD3A), σ1R-KO mouse, SOD1-ALS mouse, mitochondrial morphology analysis, Blue Native PAGE for ATAD3A oligomeric state Neurobiology of disease Medium 36736924
2024 ATAD3A interacts with PERK at mitochondria-ER contact sites. During ER stress, PERK-ATAD3A interactions increase, and ATAD3A competes with eIF2 for PERK binding, attenuating local PERK signaling and protecting active translation at mitochondria from global translational repression. ATAD3A binding to PERK thus mediates subcellular control of translational repression. Live-cell imaging of reporter mRNA translation, co-immunoprecipitation (PERK/ATAD3A/eIF2), proximity ligation assay for contact sites, ATAD3A knockdown Science High 39116259
2024 SIRT3 deacetylates ATAD3A; acetylation at K134 reduces ATAD3A self-oligomerization and promotes cardiac hypertrophy. Acetylated ATAD3A monomer interacts with the IP3R1-GRP75-VDAC1 complex at MAMs, leading to mitochondrial calcium overload. SIRT3 knockout mice show excessive MAM formation. ATAD3A oligomerization is thus regulated by SIRT3-dependent acetylation status. Co-immunoprecipitation, SIRT3 KO mouse, site-directed mutagenesis (K134), calcium imaging, MAM analysis, cardiac hypertrophy model International journal of biological sciences Medium 38250153
2024 TBK1 is abnormally activated and localizes to mitochondria during senescence, where it directly phosphorylates ATAD3A at Ser321. Phosphorylated ATAD3A suppresses PINK1-mediated mitophagy by facilitating PINK1 mitochondrial import. A blocking peptide (TAT-PEP) abrogating this phosphorylation rescues cellular senescence and enhances tumor sensitivity to chemotherapy. In vitro kinase assay (TBK1 phosphorylating ATAD3A at S321), site-directed mutagenesis (S321A), blocking peptide, senescence assays, aging mouse models Advanced science High 39520088
2024 TRIM25 E3 ubiquitin ligase interacts with and ubiquitinates ATAD3A via the proteasome pathway, reducing ATAD3A protein stability. Reduced ATAD3A allows PINK1 accumulation and activates PINK1/Parkin-dependent mitophagy. ME2 competes with TRIM25 for binding to ATAD3A, preventing ATAD3A ubiquitination and stabilizing it. Co-immunoprecipitation (TRIM25/ATAD3A), ubiquitination assay, proteasome inhibitor experiments, western blot, CI/RI rat model Free radical biology & medicine Medium 39307194
2025 FBXL6 E3 ubiquitin ligase directly targets ATAD3A and induces K63-linked polyubiquitination, stabilizing ATAD3A and activating aerobic glycolysis to promote tumor malignancy in TNBC. Co-immunoprecipitation, ubiquitination assay specifying K63-linkage, ATAD3A knockout/knockdown, in vivo xenograft International journal of biological macromolecules Medium 40975350
2025 ATAD3A directly interacts with complex I subunit NDUFS8 and plays an integral role in complex I assembly and activity. Knockdown of ATAD3A reduces complex I activity and proton leakage, increases mitochondrial membrane potential, and induces reverse electron transport (RET) that increases mitochondrial ROS production. Co-immunoprecipitation (ATAD3A/NDUFS8), complex I activity assay, ROS measurement, mitochondrial membrane potential assay, C. elegans and mammalian cell knockdown Free radical biology & medicine Medium 40961994
2025 ATAD3 is the first identified essential component of the mitochondrial permeability transition pore (mPTP). Cardiomyocyte- and hepatocyte-specific genetic deletion of Atad3 renders mitochondria incapable of Ca2+-induced mPTP-dependent swelling, yielding the highest Ca2+ retention capacity reported for any mPTP genetic perturbation. Recombinant ATAD3A reconstituted in liposomes displays intrinsic channel activity by patch-clamp. Cardiac Atad3 deletion markedly reduces infarct size following ischemia/reperfusion with no additive protection from cyclosporine A. Conditional cardiomyocyte/hepatocyte Atad3 KO, Ca2+-induced mitochondrial swelling assay, patch-clamp of ATAD3A in liposomes, I/R infarct size measurement bioRxivpreprint High bio_10.1101_2025.06.13.658955
2021 ATAD3A stabilizes GRP78 to suppress ER stress-induced unfolded protein response, providing acquired chemoresistance. Knockdown of ATAD3A dysregulates protein processing, induces ER stress, reduces surface calreticulin exposure, and sensitizes colorectal cancer cells to chemotherapy-induced immunogenic cell death. Co-immunoprecipitation (ATAD3A/GRP78), RNA-seq, siRNA knockdown, calreticulin surface exposure assay, in vivo tumor model, T-cell infiltration analysis Journal of cellular physiology Medium 33580514

Source papers

Stage 0 corpus · 58 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Recurrent De Novo and Biallelic Variation of ATAD3A, Encoding a Mitochondrial Membrane Protein, Results in Distinct Neurological Syndromes. American journal of human genetics 144 27640307
2010 The AAA+ ATPase ATAD3A controls mitochondrial dynamics at the interface of the inner and outer membranes. Molecular and cellular biology 136 20154147
2017 Atad3a suppresses Pink1-dependent mitophagy to maintain homeostasis of hematopoietic progenitor cells. Nature immunology 115 29242539
2023 Targeting ATAD3A-PINK1-mitophagy axis overcomes chemoimmunotherapy resistance by redirecting PD-L1 to mitochondria. Cell research 96 36627348
2015 Mitochondrial ATAD3A combines with GRP78 to regulate the WASF3 metastasis-promoting protein. Oncogene 82 25823022
2019 ATAD3A oligomerization causes neurodegeneration by coupling mitochondrial fragmentation and bioenergetics defects. Nature communications 80 30914652
2020 Mitophagy promotes sorafenib resistance through hypoxia-inducible ATAD3A dependent Axis. Journal of experimental & clinical cancer research : CR 78 33280610
2021 Enhanced cGAS-STING-dependent interferon signaling associated with mutations in ATAD3A. The Journal of experimental medicine 77 34387651
2021 AMBRA1 regulates mitophagy by interacting with ATAD3A and promoting PINK1 stability. Autophagy 66 34798798
2017 ATPase-deficient mitochondrial inner membrane protein ATAD3A disturbs mitochondrial dynamics in dominant hereditary spastic paraplegia. Human molecular genetics 66 28158749
2022 ATAD3A oligomerization promotes neuropathology and cognitive deficits in Alzheimer's disease models. Nature communications 63 35236834
2021 ATAD3A has a scaffolding role regulating mitochondria inner membrane structure and protein assembly. Cell reports 57 34936866
2022 The oncoprotein MUC1 facilitates breast cancer progression by promoting Pink1-dependent mitophagy via ATAD3A destabilization. Cell death & disease 51 36289190
2010 The calcium-dependent interaction between S100B and the mitochondrial AAA ATPase ATAD3A and the role of this complex in the cytoplasmic processing of ATAD3A. Molecular and cellular biology 41 20351179
2010 Topological analysis of ATAD3A insertion in purified human mitochondria. Journal of bioenergetics and biomembranes 39 20349121
2021 ATAD3A stabilizes GRP78 to suppress ER stress for acquired chemoresistance in colorectal cancer. Journal of cellular physiology 36 33580514
2024 PERK-ATAD3A interaction provides a subcellular safe haven for protein synthesis during ER stress. Science (New York, N.Y.) 33 39116259
2020 Emerging Links between Control of Mitochondrial Protein ATAD3A and Cancer. International journal of molecular sciences 32 33113782
2012 ATAD3B is a human embryonic stem cell specific mitochondrial protein, re-expressed in cancer cells, that functions as dominant negative for the ubiquitous ATAD3A. Mitochondrion 32 22664726
2022 ATAD3A mediates activation of RAS-independent mitochondrial ERK1/2 signaling, favoring head and neck cancer development. Journal of experimental & clinical cancer research : CR 30 35093151
2022 Mitochondrial nucleoid trafficking regulated by the inner-membrane AAA-ATPase ATAD3A modulates respiratory complex formation. Proceedings of the National Academy of Sciences of the United States of America 30 36383603
2020 Mitochondrial dysfunction caused by novel ATAD3A mutations. Molecular genetics and metabolism 29 32933822
2021 Functional interpretation of ATAD3A variants in neuro-mitochondrial phenotypes. Genome medicine 28 33845882
2017 Baculovirus LEF-11 Hijack Host ATPase ATAD3A to Promote Virus Multiplication in Bombyx mori cells. Scientific reports 28 28393927
2019 Novel ATAD3A recessive mutation associated to fatal cerebellar hypoplasia with multiorgan involvement and mitochondrial structural abnormalities. Molecular genetics and metabolism 27 31727539
2024 The SIRT3-ATAD3A axis regulates MAM dynamics and mitochondrial calcium homeostasis in cardiac hypertrophy. International journal of biological sciences 25 38250153
2022 Loss of mitochondrial ATPase ATAD3A contributes to nonalcoholic fatty liver disease through accumulation of lipids and damaged mitochondria. The Journal of biological chemistry 23 35513069
2019 ATAD3A on the Path to Cancer. Advances in experimental medicine and biology 20 30919342
2023 ATAD3A: A Key Regulator of Mitochondria-Associated Diseases. International journal of molecular sciences 19 37569886
2023 Sigma-1 receptor maintains ATAD3A as a monomer to inhibit mitochondrial fragmentation at the mitochondria-associated membrane in amyotrophic lateral sclerosis. Neurobiology of disease 14 36736924
2018 Mitochondrial ATAD3A regulates milk biosynthesis and proliferation of mammary epithelial cells from dairy cow via the mTOR pathway. Cell biology international 14 29286187
2021 miRNA-27a Transcription Activated by c-Fos Regulates Myocardial Ischemia-Reperfusion Injury by Targeting ATAD3a. Oxidative medicine and cellular longevity 12 34413925
2024 Ubiquitination of ATAD3A by TRIM25 exacerbates cerebral ischemia-reperfusion injury via regulating PINK1/Parkin signaling pathway-mediated mitophagy. Free radical biology & medicine 11 39307194
2019 Ketogenic diet attenuates cerebellar atrophy progression in a subject with a biallelic variant at the ATAD3A locus. The application of clinical genetics 11 31239750
2023 ATAD3A-related pontocerebellar hypoplasia: new patients and insights into phenotypic variability. Orphanet journal of rare diseases 9 37095554
2023 Harel Yoon syndrome: a novel mutation in ATAD3A gene and expansion of the clinical spectrum. Ophthalmic genetics 8 36856321
2023 Ketogenic Diet Attenuates Refractory Epilepsy of Harel-Yoon Syndrome With ATAD3A Variants: A Case Report and Review of Literature. Pediatric neurology 7 37031571
2024 Targeting ATAD3A Phosphorylation Mediated by TBK1 Ameliorates Senescence-Associated Pathologies. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 6 39520088
2022 Severe spinal cord hypoplasia due to a novel ATAD3A compound heterozygous deletion. Molecular genetics and metabolism reports 6 36061954
2023 The value of ATAD3A as a potential biomarker for bladder cancer. Cancer medicine 5 38018291
2023 Identification of ATAD3A as a key regulator in non-small cell lung cancer by promoting STAT3-induced cell proliferation and tumor angiogenesis. Molecular carcinogenesis 4 38050826
2022 Deletion of ATAD3A inhibits osteogenesis by impairing mitochondria structure and function in pre-osteoblast. Developmental dynamics : an official publication of the American Association of Anatomists 4 36000457
2012 Yeast-based production and purification of HIS-tagged human ATAD3A, A specific target of S100B. Protein expression and purification 4 22542587
2025 Thymoquinone alleviates myocardial ischemia/reperfusion injury by stabilizing mitochondria-associated membrane homeostasis via targeting ATAD3A. Phytomedicine : international journal of phytotherapy and phytopharmacology 2 40460607
2025 Empagliflozin-pretreated BMSC exosomes attenuate myocardial ischemia-reperfusion injury by enhancing atad3a/pink1-dependent mitophagy. Stem cell research & therapy 2 41163081
2023 "ATAD3C regulates ATAD3A assembly and function in the mitochondrial membrane". Free radical biology & medicine 2 38092275
2023 ATAD3A gene variations in a family with Harel-Yoon syndrome. Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 2 38105692
2023 Harel-Yoon syndrome caused by a novel variant in ATAD3A: A case report. Heliyon 2 38173481
2025 Elevated FBXL6 activates ATAD3A through K63-linked polyubiquitination and promotes the malignant progression of TNBC via metabolic reprogramming. International journal of biological macromolecules 1 40975350
2025 P4HA2 interacted with ATAD3A to modulate PINK1/parkin-dependent mitophagy and 125I brachytherapy sensitization in esophageal carcinoma. Cell death & disease 1 41053045
2020 Using Genome-Editing Tools to Develop a Novel In Situ Coincidence Reporter Assay for Screening ATAD3A Transcriptional Inhibitors. Methods in molecular biology (Clifton, N.J.) 1 32219745
2026 Single-cell transcriptomic analysis and machine learning identify ATAD3A as a key gene that stabilizes mitochondrial-endoplasmic reticulum membranes, promoting bladder cancer progression. Journal of translational medicine 0 41715136
2026 Malic enzyme 2 suppresses PINK1-Parkin-mediated mitophagy by stabilizing ATAD3A via competitive interaction with TRIM25. Cell death & disease 0 41876455
2026 ATAD3A promotes bladder cancer progression by regulating glycolysis through MYC stabilization. Journal of translational medicine 0 42001122
2025 Clinical characteristics and induced pluripotent stem cells (iPSCs) disease model of Harel-Yoon syndrome caused by compound heterozygous ATAD3A variants. Human cell 0 40246775
2025 ATAD3A deficiency induces oxidative eustress via the complex I reverse electron transport. Free radical biology & medicine 0 40961994
2025 Allele-specific correction of ATAD3A pathogenic variants via template-free CRISPR-Cas9 editing and gene conversion. bioRxiv : the preprint server for biology 0 41280066
2025 [A case of Harel-Yoon syndrome with seizures caused by an ATAD3A variant]. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 0 41401963