title: Golgi in copper homeostasis: a view from the membrane trafficking field.
abstract: Copper is essential for a variety of important biological processes as a cofactor and regulator of many enzymes. Incorporation of copper into the secreted and plasma membrane-targeted cuproenzymes takes place in Golgi, a compartment central for normal copper homeostasis. The Golgi complex harbors copper-transporting ATPases, ATP7A and ATP7B that transfer copper from the cytosol into Golgi lumen for incorporation into copper-dependent enzymes. The Golgi complex also sends these ATPases to appropriate post-Golgi destinations to ensure correct Cu fluxes in the body and to avoid potentially toxic copper accumulation. Mutations in ATP7A or ATP7B or in the proteins that regulate their trafficking affect their exit from Golgi or subsequent retrieval to this organelle. This, in turn, disrupts the homeostatic Cu balance, resulting in copper deficiency (Menkes disease) or copper overload (Wilson disease). Research over the last decade has yielded significant insights into the enzymatic properties and cell biology of the copper ATPases. However, the mechanisms through which the Golgi regulates trafficking of ATP7A/7B and, therefore, maintains Cu homeostasis remain unclear. This review summarizes current data on the role of the Golgi in Cu metabolism and outlines questions and challenges that should be addressed to understand ATP7A and ATP7B trafficking mechanisms in health and disease.
authors.affiliation: Telethon Institute of Genetics and Medicine TIGEM, Via Pietro Castellino, 111, 80131 Naples, Italy. polish@tigem.it
authors.forename: Roman
authors.initials: R
authors.lastname: Polishchuk
authors.forename: Svetlana
authors.initials: S
authors.lastname: Lutsenko
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D001692:Biological Transport; D027682:Cation Transport Proteins / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D000073840:Copper-Transporting ATPases; D006056:Golgi Apparatus / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases