ArticleScientific reports2020
Metallothioneins regulate ATP7A trafficking and control cell viability during copper deficiency and excess.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Coping with copper: a bibliometric analysis of copper's role in cancer pathogenesis and treatment.Systematic reviews · 2025Pooled it
- Copper, cuproptosis, and cancer: biology concepts of a novel cell death.Apoptosis : an international journal on programmed cell death · 2026Review
- Review
- Harnessing Cuproptosis for Antitumor Immunity: A Review of Current Evidence and Therapeutic Strategies.Molecular carcinogenesis · 2026Review
- A broad-spectrum inhibitor of copper-exporting PProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Dynamic assessment of the allocation of copper to cytochrome c oxidase using size-exclusion chromatography (SEC) combined with inductively coupled plasma mass spectrometry (ICP-MS).The Journal of biological chemistry · 2026Article
- Tackling cuproptosis: from metabolic rewiring to therapeutic exploitation in cancer.Cellular & molecular immunology · 2026Review
- A First-In-Class Broad Spectrum Inhibitor of Copper Exporting PbioRxiv : the preprint server for biology · 2026Article
- The Copper Chaperone ATOX1 Exhibits Differential Protein-Protein Interactions and Contributes to Skeletal Myoblast Differentiation.Molecular and cellular biology · 2026Article
- Ferroptosis and cuproptosis in head and neck squamous cell carcinoma: interconnected mechanisms and therapeutic implications.Frontiers in pharmacology · 2026Review
- Copper homeostasis and cuproptosis in Alzheimer's disease (Review).International journal of molecular medicine · 2025Review
- Micro- and Nanoplastics Act as Metal Carriers with the Potential to Alter Human Gene Expression Patterns-The Inferences from Bioinformatic Online Tools.Biomolecules · 2025Review
- Prokaryotic mechanosensitive channels mediate copper influx.Protein science : a publication of the Protein Society · 2025Article
- Elesclomol rescues mitochondrial copper deficiency in disease models without triggering cuproptosis.The Journal of pharmacology and experimental therapeutics · 2025Article
- Mammalian copper homeostasis: physiological roles and molecular mechanisms.Physiological reviews · 2025Review
- From copper homeostasis to cuproptosis: a new perspective on CNS immune regulation and neurodegenerative diseases.Frontiers in neurology · 2025Review
- Copper homeostasis and copper-induced cell death in tumor immunity: implications for therapeutic strategies in cancer immunotherapy.Biomarker research · 2024Review
- Molecular mechanisms and therapeutic strategies for ferroptosis and cuproptosis in ischemic stroke.Brain, behavior, & immunity - health · 2024Review
- Copper in colorectal cancer: From copper-related mechanisms to clinical cancer therapies.Clinical and translational medicine · 2024Review
- Targeting cuproplasia and cuproptosis in cancer.Nature reviews. Clinical oncology · 2024Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Copper (Cu) is an essential, yet potentially toxic nutrient, as illustrated by inherited diseases of copper deficiency and excess. Elevated expression of the ATP7A Cu exporter is known to confer copper tolerance, however, the contribution of metal-binding metallothioneins is less clear. In this study, we investigated the relative contributions of ATP7A and the metallothioneins MT-I and MT-II to cell viability under conditions of Cu excess or deficiency. Although the loss of ATP7A increased sensitivity to low Cu concentrations, the absence of MTs did not significantly affect Cu tolerance. However, the absence of all three proteins caused a synthetic lethal phenotype due to extreme Cu sensitivity, indicating that MTs are critical for Cu tolerance only in the absence of ATP7A. A lack of MTs resulted in the trafficking of ATP7A from the trans-Golgi complex in a Cu-dependent manner, suggesting that MTs regulate the delivery of Cu to ATP7A. Under Cu deficiency conditions, the absence of MTs and / or ATP7A enhanced cell proliferation compared to wild type cells, suggesting that these proteins compete with essential Cu-dependent pathways when Cu is scarce. These studies reveal new roles for ATP7A and metallothioneins under both Cu deficiency and excess.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.