ArticleThe Journal of biological chemistry2016
The Activity of Menkes Disease Protein ATP7A Is Essential for Redox Balance in Mitochondria.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 75 citations in OpenAlex.
- Trial
- The Role of Metal Ions in Mitochondria: From Energy Metabolism to Cell Destiny.Biological trace element research · 2026Review
- Copper in Human Health and Disease: Insights from Inherited Disorders.Physiology (Bethesda, Md.) · 2026Review
- Cuproptosis in inflammation and cancer: molecular mechanisms and therapeutic targets.Molecular cancer · 2026Review
- COG5 deficiency disrupts cellular copper homeostasis and underlies the impaired mitochondrial OXPHOS function.PLoS genetics · 2026Article
- High copper levels induce oxidative stress and inflammatory processes in a cell culture model of Wilson's disease.Molecular and cellular biochemistry · 2026Article
- Repurposing melatonin's therapeutic potential in Wilson disease: Addressing copper overload and redox imbalance.Redox biology · 2026Article
- Genomic insights into adaptation to bipedal saltation and desert-like habitats of jerboas.Science China. Life sciences · 2024Article
- Safety and tolerability of the protein C activator AB002 in end-stage renal disease patients on hemodialysis: a randomized phase 2 trial.Communications medicine · 2024Article
- ATP7A-dependent copper sequestration contributes to termination of β-CATENIN signaling during early adipogenesis.Molecular metabolism · 2024Article
- Augmenting MEK inhibitor efficacy in BRAF wild-type melanoma: synergistic effects of disulfiram combination therapy.Journal of experimental & clinical cancer research : CR · 2024Article
- Review
- α-lipoic acid ameliorates consequences of copper overload by up-regulating selenoproteins and decreasing redox misbalance.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Regulation of Atp7a RNA contributes to differentiation-dependent Cu redistribution in skeletal muscle cells.Metallomics : integrated biometal science · 2023Article
- Mitochondrial copper in human genetic disorders.Trends in endocrinology and metabolism: TEM · 2023Review
- Copper dependent ERK1/2 phosphorylation is essential for the viability of neurons and not glia.Metallomics : integrated biometal science · 2022Article
- Pharmacokinetics of CuGTSM, a Novel Drug Candidate, in a Mouse Model of Menkes Disease.Pharmaceutical research · 2021Article
- Autophagy deficiency exacerbates acute lung injury induced by copper oxide nanoparticles.Journal of nanobiotechnology · 2021Article
- Review
- Skin Pigmentation Abnormalities and Their Possible Relationship with Skin Aging.International journal of molecular sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Copper-transporting ATPase ATP7A is essential for mammalian copper homeostasis. Loss of ATP7A activity is associated with fatal Menkes disease and various other pathologies. In cells, ATP7A inactivation disrupts copper transport from the cytosol into the secretory pathway. Using fibroblasts from Menkes disease patients and mouse 3T3-L1 cells with a CRISPR/Cas9-inactivated ATP7A, we demonstrate that ATP7A dysfunction is also damaging to mitochondrial redox balance. In these cells, copper accumulates in nuclei, cytosol, and mitochondria, causing distinct changes in their redox environment. Quantitative imaging of live cells using GRX1-roGFP2 and HyPer sensors reveals highest glutathione oxidation and elevation of H2O2 in mitochondria, whereas the redox environment of nuclei and the cytosol is much less affected. Decreasing the H2O2 levels in mitochondria with MitoQ does not prevent glutathione oxidation; i.e. elevated copper and not H2O2 is a primary cause of glutathione oxidation. Redox misbalance does not significantly affect mitochondrion morphology or the activity of respiratory complex IV but markedly increases cell sensitivity to even mild glutathione depletion, resulting in loss of cell viability. Thus, ATP7A activity protects mitochondria from excessive copper entry, which is deleterious to redox buffers. Mitochondrial redox misbalance could significantly contribute to pathologies associated with ATP7A inactivation in tissues with paradoxical accumulation of copper (i.e. renal epithelia).
Indexed as
Identifiers
What OpenQuestion holds
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.