Ask about this productRelated genes to: COMMD1 Blocking Peptide
- Gene:
- COMMD1 NIH gene
- Name:
- copper metabolism domain containing 1
- Previous symbol:
- C2orf5
- Synonyms:
- MURR1, MGC27155
- Chromosome:
- 2p15
- Locus Type:
- gene with protein product
- Date approved:
- 2003-08-26
- Date modifiied:
- 2016-01-07
Related products to: COMMD1 Blocking Peptide
Related articles to: COMMD1 Blocking Peptide
- - Source: PubMed
Publication date: 2026/07/31
Luo JingjingZhang XiaolingBharati LaxmanHua ZiyuChen ShaDong Zhi - Superoxide dismutase 1 (SOD1), a copper-dependent antioxidant, is essential for redox homeostasis, and its decline drives renal senescence and fibrosis. However, the mechanisms linking profibrotic signaling to SOD1 inhibition remain unclear. Here, we identified a pathological copper-COMMD1-SOD1 axis in which intracellular copper overload paradoxically suppressed SOD1 activity. In kidney tissues from chronic kidney disease (CKD) patients and complementary in vivo and in vitro fibrotic models, we consistently observed a reduction in SOD1 activity accompanied by elevated intracellular copper levels. Lowering intracellular copper levels restored SOD1 activity, suppressed reactive oxygen species (ROS) accumulation, and alleviated cell senescence and fibrosis. Mechanistically, pathological copper overload impaired SOD1 homodimerization, the essential final step in its activation. We identified copper metabolism MURR1 domain containing 1 (COMMD1) as a key copper-sensitive mediator of this process. Copper overload acted upstream, simultaneously upregulating COMMD1 expression and enhancing its binding affinity to SOD1. This enhanced COMMD1-SOD1 interaction directly disrupted SOD1 homodimer assembly and enzymatic function. Collectively, these findings redefined the regulatory role of copper in SOD1 activity and uncovered a previously unrecognized mechanism by which pathological copper overload paradoxically suppressed SOD1 activity via COMMD1-dependent disruption of SOD1 homodimerization, providing new insight into the pathophysiology of copper dyshomeostasis-associated diseases. - Source: PubMed
Publication date: 2026/07/02
Liu YuqingLiu JingZhou WenqianNiu YangyangZheng YanLiu YiguoZhang YingyingYu Chen - Copper (Cu) homeostasis dysregulation is one of the key factor exacerbating mitochondrial dysfunction and impairing cardiac repair in myocardial infarction (MI). Herein, by integrating single-cell transcriptomics, clinical specimens, and animal models, we first identified COMMD1 as a key negative regulator of Cu homeostasis in MI. We then constructed a Cu nanoregulator, Qu@Cu-SS31, that selectively accumulate in the mitochondria of ischemic cardiomyocytes and release bioactive Cu in a pH-responsive manner, enhancing mitochondrial function and promoting myocardial recovery. Mechanistic studies revealed that Qu@Cu-SS31 mediated significant downregulation of COMMD1, concomitant with downregulation of Cu transporters CTR1 and CCS. Additionally, Qu@Cu-SS31 showed robust reactive oxygen species scavenging ability. This COMMD1-Cu-ROS regulatory axis potently inhibited NLRP3-Caspase-1 dependent pyroptosis, and apoptosis via rebalance of Bcl-2/Bax expression. In a mice MI model, Qu@Cu-SS31 exhibited preferential accumulation in infarcted regions, leading to significant functional recovery, reduced infarct size, and enhanced tissue regeneration. Our work establishes a novel nanoregulator for Cu homeostasis restoration and illustrates the critical role of COMMD1 downregulation in mitigating mitochondrial damage, highlighting the therapeutic potential of Cu homeostasis regulation in cardiovascular applications. - Source: PubMed
Publication date: 2026/06/02
Zang QingluQin ZhenOu JianliangWang MingkangZhou LinglingZhou JiaYang XingyuShen RulingWang KaiyangLuo YuWu HuixiaMou JuanWu JianrongCai XiaojunDu WenxianZheng YuanyiLi Yuehua - Mutations in superoxide dismutase 1 (SOD1) compromise its metal-binding capacity, resulting in protein misfolding and aggregation, which ultimately induces cellular apoptosis in amyotrophic lateral sclerosis (ALS). Copper metabolism domain containing 1 (COMMD1), a gene implicated in copper homeostasis, has not been thoroughly characterized in the context of ALS pathogenesis. In this study, we identified elevated COMMD1 expression in ALS, potentially contributing to diminished copper incorporation into SOD1. Knockdown of COMMD1 enhanced palmitoylation of the copper chaperone for SOD1 (CCS), facilitating its membrane translocation and promoting copper loading into SOD1, thereby conferring neuroprotection in ALS. Mechanistically, we established that COMMD1 knockdown augments CCS palmitoylation via activation of the hypoxia-inducible factor 1 subunit alpha (HIF-1α)/fatty acid synthase (FASN) signaling axis. In vivo investigations utilizing male hSOD1 transgenic mice demonstrated that COMMD1 deficiency markedly ameliorated the deterioration of motor function and prolonged survival duration. These findings collectively suggest that COMMD1 represents a potential therapeutic target for ALS intervention. - Source: PubMed
Publication date: 2026/06/17
Su XiaoliTan XingliWang YingLiang WeiweiWang DiHuo DiWang HongyongQi YanZhang WenmoHan LingZhang DongmeiWang MingXu JingWang ShuyuWang JingFeng Honglin - Intervertebral disc degeneration (IDD) is a major cause of low back pain, yet the biological effects of commonly used non-steroidal anti-inflammatory drugs (NSAIDs) on disc cells remain poorly understood. Celecoxib is widely prescribed for IDD-related pain, but its direct influence on IDD has not been systematically examined. Here, we identify a concentration-dependent biphasic effect of celecoxib on nucleus pulposus (NP) cells and uncover the mechanism that converts celecoxib from protective to detrimental. Using interleukin-1β-stimulated NP cells and rat IDD models, we show that low-dose celecoxib (≤20 µm) suppresses inflammation and preserves extracellular matrix (ECM). In contrast, high-dose celecoxib (>20 µm) activates a previously unrecognized heat shock protein 90 (HSP90)/RING-box protein 1 (RBX1)/cuproptosis axis, leading to copper accumulation, mitochondrial stress, and ECM degradation. Mechanistically, elevated celecoxib induces HSP90 upregulation, which stabilizes RBX1 by reducing its K48-linked ubiquitination. Accumulated RBX1 promotes ATPase copper transporting beta (ATP7B) and its regulator copper metabolism domain containing 1 (COMMD1) degradation, thereby triggering cuproptosis. Pharmacologic inhibition of HSP90 or cuproptosis effectively reverses the detrimental effects of high-dose celecoxib in vivo. Together, these findings define a strict therapeutic window for celecoxib in IDD and reveal a novel HSP90/RBX1-mediated cuproptosis pathway that mediates its dual effects. - Source: PubMed
Publication date: 2026/05/04
Guo YoufengXiao HongjuBa ShenghaoZhou YuWang BijunYu BinHuang YufengZhao HaihongChen Zhefan StephenShen NaBa ZhaoyuWu Desheng