Molecular mechanisms of copper homeostasis.
The transition metal copper (Cu) is an essential trace element for all biota. Its redox properties bestow Cu with capabilities that are simultaneously essential and potentially damaging to the cell. Free Cu is virtually absent in the cell. The descriptions of the structural and functional organization of the metallothioneins, Cu-chaperones and P-type ATPases as well as of the mechanisms that regulate their distribution and functioning in the cell have enormously advanced our understanding of the Cu homeostasis and metabolism in the last decade. Cu is stored by metallothioneins and distributed by specialized chaperones to specific cell targets that make use of its redox properties. Transfer of Cu to newly synthesized cuproenzymes and Cu disposal is performed by the individual or concerted actions of the P-type ATPases ATP7A and ATP7B expressed in tissues. In mammalians liver is the major captor, distributor and excreter of Cu. Mutations in the P-type ATPases that interfere with their functioning and traffic are cause of the life-threatening Wilson (ATP7B) and Menkes (ATP7A) diseases.
Lalioti
Vasiliki
V
Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid, Cantoblanco 28049, Madrid, Spain.
Muruais
Gemma
G
Tsuchiya
Yo
Y
Pulido
Diego
D
Sandoval
Ignacio V
IV
D000251:Adenosine Triphosphatases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000818:Animals; D027682:Cation Transport Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D003300:Copper / Q000008:administration & dosage / Q000172:deficiency / Q000378:metabolism* / Q000493:pharmacokinetics; D000073840:Copper-Transporting ATPases; D004032:Diet; D003576:Electron Transport Complex IV / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006527:Hepatolenticular Degeneration / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008099:Liver / Q000378:metabolism; D007706:Menkes Kinky Hair Syndrome / Q000235:genetics / Q000378:metabolism; D008668:Metallothionein / Q000378:metabolism; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism; D009154:Mutation; D010084:Oxidation-Reduction; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1
D027682:Cation Transport Proteins; D018832:Molecular Chaperones; C000606290:SOD1 protein, human; D003300:Copper; D008668:Metallothionein; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D003576:Electron Transport Complex IV; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases; D005978:Glutathione