ArticleHuman molecular genetics2017
The mitochondrial metallochaperone SCO1 maintains CTR1 at the plasma membrane to preserve copper homeostasis in the murine heart.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 32 citations in OpenAlex.
- Pathogenic variants of the mitochondrial copper chaperones SCO1 and SCO2 reshape their respective interactomes and disrupt cellular phospholipid metabolism.bioRxiv : the preprint server for biology · 2026Article
- Copper transport to mitochondria by SLC25A3 contributes to skeletal myoblast differentiation and is required for survival of differentiated myotubes.bioRxiv : the preprint server for biology · 2026Article
- Mutant CHCHD10 disrupts cytochrome c oxidation and activates mitochondrial retrograde signaling.EMBO molecular medicine · 2026Article
- Role of Copper Homeostasis and Cuproptosis in Cardiovascular Disease: Molecular Insights and Metabolic Perspectives.International journal of biological sciences · 2026Review
- A systems genetics approach to uncover mitochondrial drivers of heart failure reveals mitochondria-nuclear cross talk in genetically diverse mouse strains.bioRxiv : the preprint server for biology · 2025Article
- Heart is the most susceptible organ in an isogenic background to loss of function mutations in the mitochondrial metallochaperone SCO1.Human molecular genetics · 2025Article
- Elevated COMMD1 Contributes to Cardiomyocyte Copper Efflux in Chronic Myocardial Ischemia: Insights From Rhesus Monkey.Cell proliferation · 2025Article
- [Role and mechanism of copper overload-mediated endoplasmic reticulum stress in vascular endothelial injury in Kawasaki disease].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2025Article
- Article
- Mammalian copper homeostasis: physiological roles and molecular mechanisms.Physiological reviews · 2025Review
- Endocrinological features and epileptic encephalopathy in COX deficiency due to SCO1 mutations: case series and review of literature.Endocrine connections · 2024Article
- Dexmedetomidine enables copper homeostasis in cerebral ischemia/reperfusion via ferredoxin 1.Annals of medicine · 2023Article
- A yeast suppressor screen links Coa4 to the mitochondrial copper delivery pathway for cytochrome c oxidase.Genetics · 2022Article
- Review
- Mitochondrial CytochromeFrontiers in cell and developmental biology · 2022Article
- Prime Real Estate: Metals, Cofactors and MICOS.Frontiers in cell and developmental biology · 2022Review
- Dynamic and cell-specific transport networks for intracellular copper ions.Journal of cell science · 2021Review
- Toxic effects of metal copper stress on immunity, metabolism and pathologic changes in Chinese mitten crab (Eriocheir japonica sinensis).Ecotoxicology (London, England) · 2021Article
- Getting out what you put in: Copper in mitochondria and its impacts on human disease.Biochimica et biophysica acta. Molecular cell research · 2021Review
- Metabolic Alterations in Inherited Cardiomyopathies.Journal of clinical medicine · 2019Review
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
SCO1 is a ubiquitously expressed, mitochondrial protein with essential roles in cytochrome c oxidase (COX) assembly and the regulation of copper homeostasis. SCO1 patients present with severe forms of early onset disease, and ultimately succumb from liver, heart or brain failure. However, the inherent susceptibility of these tissues to SCO1 mutations and the clinical heterogeneity observed across SCO1 pedigrees remain poorly understood phenomena. To further address this issue, we generated Sco1hrt/hrt and Sco1stm/stm mice in which Sco1 was specifically deleted in heart and striated muscle, respectively. Lethality was observed in both models due to a combined COX and copper deficiency that resulted in a dilated cardiomyopathy. Left ventricular dilation and loss of heart function was preceded by a temporal decrease in COX activity and copper levels in the longer-lived Sco1stm/stm mice. Interestingly, the reduction in copper content of Sco1stm/stm cardiomyocytes was due to the mislocalisation of CTR1, the high affinity transporter that imports copper into the cell. CTR1 was similarly mislocalized to the cytosol in the heart of knockin mice carrying a homozygous G115S substitution in Sco1, which in humans causes a hypertrophic cardiomyopathy. Our current findings in the heart are in marked contrast to our prior observations in the liver, where Sco1 deletion results in a near complete absence of CTR1 protein. These data collectively argue that mutations perturbing SCO1 function have tissue-specific consequences for the machinery that ultimately governs copper homeostasis, and further establish the importance of aberrant mitochondrial signaling to the etiology of copper handling disorders.
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