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Copper homeostasis and the ubiquitin proteasome system

Copper is involved in many physiological pathways and important biological processes as a cofactor of several copper-dependent enzymes. Given the requirement for copper and its potential toxicity, intracellular copper levels are tightly controlled. Disturbances of human copper homeostasis are charac...

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Detalles Bibliográficos
Autores principales: Zhang, Bichao, Burke, Richard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10022722/
https://www.ncbi.nlm.nih.gov/pubmed/36822629
http://dx.doi.org/10.1093/mtomcs/mfad010
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author Zhang, Bichao
Burke, Richard
author_facet Zhang, Bichao
Burke, Richard
author_sort Zhang, Bichao
collection PubMed
description Copper is involved in many physiological pathways and important biological processes as a cofactor of several copper-dependent enzymes. Given the requirement for copper and its potential toxicity, intracellular copper levels are tightly controlled. Disturbances of human copper homeostasis are characterized by disorders of copper overload (Wilson’s disease) or copper deficiency (Menkes disease). The maintenance of cellular copper levels involves numerous copper transporters and copper chaperones. Recently, accumulating evidence has revealed that components of the ubiquitin proteasome system (UPS) participate in the posttranslational regulation of these proteins, suggesting that they might play a role in maintaining copper homeostasis. Cellular copper levels could also affect the activity of the UPS, indicating that copper homeostasis and the UPS are interdependent. Copper homeostasis and the UPS are essential to the integrity of normal brain function and while separate links between neurodegenerative diseases and UPS inhibition/copper dyshomeostasis have been extensively reported, there is growing evidence that these two networks might contribute synergistically to the occurrence of neurodegenerative diseases. Here, we review the role of copper and the UPS in the development of Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, and discuss the genetic interactions between copper transporters/chaperones and components of the UPS.
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spelling pubmed-100227222023-03-18 Copper homeostasis and the ubiquitin proteasome system Zhang, Bichao Burke, Richard Metallomics Critical Review Copper is involved in many physiological pathways and important biological processes as a cofactor of several copper-dependent enzymes. Given the requirement for copper and its potential toxicity, intracellular copper levels are tightly controlled. Disturbances of human copper homeostasis are characterized by disorders of copper overload (Wilson’s disease) or copper deficiency (Menkes disease). The maintenance of cellular copper levels involves numerous copper transporters and copper chaperones. Recently, accumulating evidence has revealed that components of the ubiquitin proteasome system (UPS) participate in the posttranslational regulation of these proteins, suggesting that they might play a role in maintaining copper homeostasis. Cellular copper levels could also affect the activity of the UPS, indicating that copper homeostasis and the UPS are interdependent. Copper homeostasis and the UPS are essential to the integrity of normal brain function and while separate links between neurodegenerative diseases and UPS inhibition/copper dyshomeostasis have been extensively reported, there is growing evidence that these two networks might contribute synergistically to the occurrence of neurodegenerative diseases. Here, we review the role of copper and the UPS in the development of Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, and discuss the genetic interactions between copper transporters/chaperones and components of the UPS. Oxford University Press 2023-02-23 /pmc/articles/PMC10022722/ /pubmed/36822629 http://dx.doi.org/10.1093/mtomcs/mfad010 Text en © The Author(s) 2023. Published by Oxford University Press. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Critical Review
Zhang, Bichao
Burke, Richard
Copper homeostasis and the ubiquitin proteasome system
title Copper homeostasis and the ubiquitin proteasome system
title_full Copper homeostasis and the ubiquitin proteasome system
title_fullStr Copper homeostasis and the ubiquitin proteasome system
title_full_unstemmed Copper homeostasis and the ubiquitin proteasome system
title_short Copper homeostasis and the ubiquitin proteasome system
title_sort copper homeostasis and the ubiquitin proteasome system
topic Critical Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10022722/
https://www.ncbi.nlm.nih.gov/pubmed/36822629
http://dx.doi.org/10.1093/mtomcs/mfad010
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