ATAD3A
- Known as:
- ATAD3A
- Catalog number:
- 002109A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- ATAD3A
Related genes to: ATAD3A
- Gene:
- ATAD3A NIH gene
- Name:
- ATPase family AAA domain containing 3A
- Previous symbol:
- -
- Synonyms:
- FLJ10709
- Chromosome:
- 1p36.33
- Locus Type:
- gene with protein product
- Date approved:
- 2004-03-24
- Date modifiied:
- 2019-01-18
Related products to: ATAD3A
Related articles to: ATAD3A
- Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer, with limited therapeutic options and dismal prognosis. Histone methyltransferase NSD2 and its catalytic product H3K36me2 are established drivers of TNBC metastasis; however, the downstream effectors linking epigenetic regulation to cellular senescence remain largely unknown. This study utilized transcriptomic profiling, ChIP-qPCR, and in vivo xenograft models to define the function and molecular mechanism of the NSD2-ATAD3A axis. We found that NSD2 was upregulated in metastatic TNBC and associated with worse survival. NSD2 directly activated ATAD3A transcription via H3K36me2 enrichment at the ATAD3A promoter. The NSD2-ATAD3A axis interacted with Drp1, triggering mitochondrial fragmentation, respiratory chain dysfunction, and lactate accumulation. Elevated lactate further induced HMGB1 lactylation and enhanced its protein stability, which sequentially activated senescence-associated genes and the senescence-associated secretory phenotype (SASP), consequently promoting epithelial-mesenchymal transition (EMT) and tumor progression. The NSD2 inhibitor KTX-1001 combined with ATAD3A knockdown enhanced the suppression of tumor burden and invasive potential with favorable biosafety.enhancedenhanced This study identifies a novel NSD2-H3K36me2-ATAD3A-Drp1-HMGB1 lactylation axis that drives senescence-associated progression in TNBC, providing a promising epigenetic-metabolic combination therapeutic strategy for this disease. - Source: PubMed
Publication date: 2026/10/01
Lin WeiChen JinshuWu KunlinZhang HuihaoYu ZhaomeiChen Xiangjin - We previously discovered that a variant p.R528W in , encoding a mitochondrial membrane-anchored protein, causes a human neurological syndrome. While mutations induce aberrant lysosomal expansion accompanied by undigested material in the lysosomes, how mutant disrupts lysosomal homeostasis and whether this contributes to neurodevelopmental defects remain unknown. Here we show that pathogenic ATAD3A p.R528W expression disrupts the mTORC1-TFEB axis as revealed by dysregulation of mTORC1 substrate phosphorylation, TFEB nuclear localization, and CLEAR gene activation associated with lysosomal biogenesis. ATAD3A binds to lysosome-localized Rag C/D GTPases, which constitute a platform for TFEB recruitment, with pathogenic variants increasing this association and thereby decreasing lysosomal localization of Rag GTPases. Importantly, overexpression of or restores TFEB phosphorylation in human cells expressing p.R528W, and overexpression or knockdown rescues lysosomal expansion and neurodevelopmental defects in . These data indicate that disrupted Rag GTPase recruitment to lysosomes and subsequent aberrant TFEB/Mitf activation contribute to neurodevelopmental and lysosomal phenotypes caused by pathogenic mutations in . Our work reveals a novel role for the mitochondrial resident protein ATAD3A in modulating lysosomal homeostasis through regulation of the mTORC1-TFEB axis, providing a mechanistic link between impaired mitochondrial and lysosomal homeostasis in a neurodevelopmental disorder. - Source: PubMed
Publication date: 2026/09/25
McDougal Mathew BSandoval AbigailKinter MikeJain AntrixLee SukyeongJung Sung YunYoon Wan Hee - Mitochondrial function depends on the maintenance of its genome, and disruptions in copy number and distribution are hallmarks of mitochondrial disorders. Mitochondrial DNA (mtDNA) replication is spatially and temporally linked to mitochondrial division (i.e., fission). However, the signal that coordinates these two events, which are physically separated by the barrier of two mitochondrial membranes, remains unknown. To gain insight into this coordination, we employed correlative cryo-electron tomography (cryo-ET) to analyze the microenvironment surrounding replicating nucleoids. Mitochondrial regions containing replicating mtDNA exhibit a unique membrane architecture defined by the presence of clustered, membrane-spanning tethers that traverse the inner membrane space. Using a combination of superresolution microscopy and genetically encoded cryo-ET tagging technology, we identify these tethers as the AAA+ ATPase ATAD3A. We further show that ATAD3A knockdown reduces recruitment of the mitochondrial fission machinery, whereas overexpression promotes its recruitment and subsequent fission. Our work suggests that ATAD3A forms nanoscale linkages that coordinate these two distinct processes, revealing a new structural paradigm for organellar communication across distinct membrane-defined environments. - Source: PubMed
Publication date: 2026/06/25
Dua NitishMa BoyuanOviedo SamanthaRahmani HamidrezaBoyd TumaraPark DonghyunWiseman R LukeGrotjahn Danielle A - Triple-negative breast cancer (TNBC) represents the most aggressive form of breast cancer and is associated with the worst prognosis. Ferroptosis holds great promise as an emerging therapeutic strategy; however, TNBC cells demonstrate reduced sensitivity to ferroptosis as a result of elevated mitochondrial membrane potential (MMP), inadequate production of reactive oxygen species (ROS), and the presence of activated antioxidant defencses, making it difficult for lipid peroxidation to accumulate to a lethal threshold. As an emerging therapeutic strategy, sonodynamic therapy (SDT) is particularly suitable for deep-seated tumors due to the excellent tissue penetration capabilities of ultrasound (US). Nevertheless, current sonosensitizer typically experience limited sonodynamic efficacy and inadequate targeting of tumors, whereas small interfering RNA (siRNA) presents a highly promising option for gene therapy, its efficacy is heavily dependent on efficient and safe cellular delivery vectors. Therefore, we designed and synthesized a folate-modified Fe-TCPP metal-organic framework (FTFA) nanoplatform that serves both as a siATAD3A gene therapy carrier and as a sonosensitizer to generate ROS upon ultrasound (US) irradiation. ATAD3A displays high expression levels in TNBC and is linked to a negative prognosis; it's silencing reduces MMPs and increases ROS-induced apoptosis. siATAD3A was loaded onto FTFA to prepare FTFA@siATAD3A, which was delivered to TNBC cells via folate receptor-mediated targeting. Under US irradiation, the Fe3+ loaded within this platform synergistically triggers a ferroptosis cascade involving the Fenton reaction, lipid peroxidation, and GPX4 downregulation, effectively inducing ferroptosis. This method greatly reduces the proliferation of cells, as well as their migration and tumor growth when tested in living organisms, and it also shows excellent compatibility with biological tissues. In summary, FTFA@siATAD3A provides a novel strategy for the synergistic gene-ferroptosis therapy of TNBC using sonodynamic effects. - Source: PubMed
Du YangYang JiangnanChen ShuaiYang XiaoxinWang YianYang YiyuanFu Deyuan - Acute kidney injury (AKI) is a clinical syndrome associated with severe morbidity and high mortality, for which there are no currently effective therapies. Aging, a state associated with Klotho protein decline, is an independent risk factor for AKI development and progression. Here, we report that Klotho-derived peptide 1 (KP1), a small peptide that recapitulates the renoprotective potential of Klotho, effectively protects against AKI in mouse models induced by either cisplatin or ischemia-reperfusion injury. KP1 treatment improved kidney function, ameliorated structural damage, inhibited tubular cell apoptosis, and preserved mitochondrial integrity in both models. Mechanistically, KP1 entered kidney proximal tubular epithelial cells via endocytosis, directly targeted the mitochondrial protein ATPase family AAA domain-containing protein 3A (ATAD3A), and prevented its degradation, and preserved its function. By interacting with the hypoxia inducible gene 1 (HIG1) domain family member 2A (HIGD2A) and maintaining its expression and function within the mitochondria, ATAD3A prevented cytochrome c release and inhibited caspase activation following injury, thereby alleviating renal tubular cell apoptosis. Collectively, these studies demonstrate that KP1 is a promising therapeutic agent for AKI by directly targeting and preserving mitochondrial integrity. Our findings also lay the groundwork for developing novel therapeutic strategies to treat diseases associated with mitochondrial dysfunction. - Source: PubMed
Publication date: 2026/08/25
Zhang XiaoyaoLin ShihuiWu TianyuZhang ZhixinZhou HongHong XueLiu Youhua