intracellular copper ion homeostasis

Definition

Target type: biologicalprocess

A homeostatic process involved in the maintenance of a steady state level of copper ions within a cell. [GOC:ai, GOC:mah]

Intracellular copper ion homeostasis is a tightly regulated process that ensures the appropriate levels of this essential metal within cells. Copper is a crucial cofactor for numerous enzymes involved in vital biological processes, including respiration, antioxidant defense, neurotransmission, and iron metabolism. However, at elevated concentrations, copper can become toxic, generating reactive oxygen species that damage cellular components. Therefore, maintaining copper homeostasis is critical for cell survival and function.

The regulation of intracellular copper levels involves a complex interplay of uptake, efflux, storage, and trafficking mechanisms.

**Copper Uptake:** Copper enters the cell through specialized transmembrane transporters. The major copper importer in mammals is CTR1 (copper transporter 1), a high-affinity transporter localized in the plasma membrane. CTR1 mediates copper uptake from the extracellular environment and delivers it to the cytoplasm.

**Copper Chaperones:** Once inside the cell, copper ions are immediately bound by specific chaperone proteins, such as ATOX1 (antioxidant protein 1), CCS (copper chaperone for superoxide dismutase), and COX17. These chaperones prevent copper from accumulating in the cytoplasm and facilitate its delivery to specific target proteins.

**Copper Storage:** For long-term storage, copper is incorporated into the copper storage protein metallothionein (MT). MT is a small, cysteine-rich protein that can bind multiple copper ions, sequestering them from the cytoplasm and preventing their toxic effects.

**Copper Trafficking:** Once bound to chaperones, copper is directed to specific intracellular compartments, including mitochondria, Golgi apparatus, and the nucleus. Specialized copper transporters, such as ATP7A and ATP7B, are responsible for transporting copper to these organelles.

**Copper Efflux:** Excess copper is extruded from the cell by the ATPases ATP7A and ATP7B. These proteins are located in the trans-Golgi network and are responsible for exporting copper into the extracellular space or delivering it to lysosomes for degradation.

**Regulation of Copper Homeostasis:** The expression and activity of copper transporters, chaperones, and storage proteins are tightly regulated to maintain copper homeostasis. Transcriptional regulation by the metal response element (MRE) is a major mechanism for controlling copper homeostasis. The MRE is a specific DNA sequence that is recognized by transcription factors that respond to changes in intracellular copper levels. In addition to transcriptional regulation, copper homeostasis is also regulated by post-translational modifications, including phosphorylation and ubiquitination.

**Dysregulation of Copper Homeostasis:** Disturbances in copper homeostasis can lead to a wide range of human diseases, including Wilson's disease, Menkes disease, and Alzheimer's disease. These diseases are caused by mutations in genes encoding copper transporters or chaperones, leading to either copper accumulation or deficiency in specific tissues.

Overall, intracellular copper ion homeostasis is a tightly regulated process that ensures the appropriate levels of this essential metal within cells. This delicate balance is maintained by a complex network of transporters, chaperones, storage proteins, and regulatory mechanisms that work together to prevent copper toxicity and ensure its proper delivery to target proteins.'
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Proteins (3)

Compounds (170)