COA4 Human
Description
Role in Cytochrome c Oxidase Assembly
COA4 facilitates copper delivery to the Cu site of Cox1, a core subunit of CcO:
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Genetic Interaction with Cox11: Overexpression of Cox11, a copper metallochaperone, rescues CcO assembly defects in coa4Δ yeast mutants by restoring Cox1 and Cox2 subunit stability .
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Copper Homeostasis: coa4Δ cells exhibit reduced cellular copper levels, impairing CcO activity. Exogenous copper supplementation partially restores respiratory function .
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Hierarchical Function: COA4 acts upstream of Cox11 in the copper delivery pathway, as shown by reciprocal regulation of their mitochondrial abundance .
Evolutionary Conservation
Human COA4 functionally complements yeast coa4Δ mutants:
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Sequence Homology: 22.3% identity and 44.7% similarity between yeast and human COA4, with conserved twin CXC motifs .
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Rescue Experiments: Expression of human COA4 in yeast restores CcO assembly, Cox1/2 stability, and respiratory growth (Fig. 1) .
Antibodies and Recombinant Proteins
Mechanistic Insights from Yeast Models
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Copper Dependency: coa4Δ mutants show reduced mitochondrial oxygen consumption rates (OCR), reversible by Cox11 overexpression or copper supplementation .
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Phenotypic Rescue: Human COA4 restores CcO supercomplex formation and mitochondrial respiration in yeast, confirming functional conservation .
Implications for Human Health
While direct links to human diseases remain under investigation, COA4’s role in copper homeostasis mirrors phenotypes observed in mitochondrial disorders:
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Copper Deficiency: Similar to SCO1/SCO2 mutations, COA4 dysfunction may disrupt cellular copper distribution, affecting CcO-dependent tissues like neurons and muscles .
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Therapeutic Potential: Modulating COA4 activity could address copper-related defects in CcO assembly, relevant for neurodegenerative and metabolic diseases .
Product Specs
Product Science Overview
Cytochrome c oxidase is a large transmembrane protein complex found in the mitochondria of eukaryotes. It is composed of multiple subunits, including two hemes (cytochrome a and cytochrome a3) and two copper centers (CuA and CuB) . The enzyme facilitates the transfer of electrons from cytochrome c to molecular oxygen, ultimately producing water and contributing to the proton gradient used by ATP synthase to generate ATP .
COA4 is involved in the proper assembly and stabilization of this complex. It ensures that the various subunits and cofactors are correctly positioned and functional . This assembly process is vital for the efficient functioning of the electron transport chain and, consequently, for cellular respiration and energy production .
Mutations or deficiencies in COA4 can lead to various mitochondrial disorders. For instance, COA4 has been associated with Bardet-Biedl Syndrome 18 and Spinal Cord Primitive Neuroectodermal Neoplasm . These conditions highlight the importance of COA4 in maintaining mitochondrial function and overall cellular health.
Human recombinant COA4 is used in research to study its role in mitochondrial function and its potential implications in various diseases. By understanding how COA4 contributes to the assembly of cytochrome c oxidase, scientists can develop targeted therapies for mitochondrial disorders and improve our understanding of cellular energy metabolism .
