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With the assistance of specific Cu chaperones, intracellular Cu(I) are transported to the specific metabolic processes in cytoplasm and nucleus through activating the target enzymes: antioxidant-1 (ATOX1) carries Cu(I) to nucleus (gene regulation) and Golgi apparatus (protein folding), copper chaperone for superoxide dismutase (CCS) carries Cu(I) to superoxide dismutase (SOD) (redox homeostasis), and cytochrome c oxidase 17 (COX17) carries Cu(I) to mitochondria (mitochondrial respiration) (Figure 1) ( FIGURE 1 Cu-dependent cell death found in 2022 is a novel non-apoptotic programmed cell death, which accelerates the development of field of Cu homeostasis imbalance

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