Coordination chemistry of mitochondrial copper metalloenzymes: exploring implications for copper dyshomeostasis in cell death
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Mitochondria, fundamental cellular organelles that govern energymetabolism, hold a pivotal role in cellular vitality. Whileconsuming dioxygen to produce adenosine triphosphate (ATP),the electron transfer process within mitochondria can engenderthe formation of reactive oxygen species that exert dual rolesin endothelial homeostatic signaling and oxidative stress. Inthe context of the intricate electron transfer process, severalmetal ions that include copper, iron, zinc, and manganeseserve as crucial cofactors in mitochondrial metalloenzymes tomediate the synthesis of ATP and antioxidant defense. In thismini review, we provide a comprehensive understanding ofthe coordination chemistry of mitochondrial cuproenzymes. Indetail, cytochrome c oxidase (CcO) reduces dioxygen to watercoupled with proton pumping to generate an electrochemicalgradient, while superoxide dismutase 1 (SOD1) functions in detoxifyingsuperoxide into hydrogen peroxide. With an emphasison the catalytic reactions of the copper metalloenzymes and insightsinto their ligand environment, we also outline the metalationprocess of these enzymes throughout the copper traffickingsystem. The impairment of copper homeostasis can triggermitochondrial dysfunction, and potentially lead to the developmentof copper-related disorders. We describe the currentknowledge regarding copper-mediated toxicity mechanisms,thereby shedding light on prospective therapeutic strategies forpathologies intertwined with copper dyshomeostasis.
Abstract
Mitochondria, fundamental cellular organelles that govern energymetabolism, hold a pivotal role in cellular vitality. Whileconsuming dioxygen to produce adenosine triphosphate (ATP),the electron transfer process within mitochondria can engenderthe formation of reactive oxygen species that exert dual rolesin endothelial homeostatic signaling and oxidative stress. Inthe context of the intricate electron transfer process, severalmetal ions that include copper, iron, zinc, and manganeseserve as crucial cofactors in mitochondrial metalloenzymes tomediate the synthesis of ATP and antioxidant defense. In thismini review, we provide a comprehensive understanding ofthe coordination chemistry of mitochondrial cuproenzymes. Indetail, cytochrome c oxidase (CcO) reduces dioxygen to watercoupled with proton pumping to generate an electrochemicalgradient, while superoxide dismutase 1 (SOD1) functions in detoxifyingsuperoxide into hydrogen peroxide. With an emphasison the catalytic reactions of the copper metalloenzymes and insightsinto their ligand environment, we also outline the metalationprocess of these enzymes throughout the copper traffickingsystem. The impairment of copper homeostasis can triggermitochondrial dysfunction, and potentially lead to the developmentof copper-related disorders. We describe the currentknowledge regarding copper-mediated toxicity mechanisms,thereby shedding light on prospective therapeutic strategies forpathologies intertwined with copper dyshomeostasis.
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