title: [4Fe-4S] Cluster Assembly in Mitochondria and Its Impairment by Copper.
abstract: The cellular toxicity of copper is usually associated with its ability to generate reactive oxygen species. However, recent studies in bacterial organisms showed that copper toxicity is also strictly connected to iron-sulfur cluster proteins and to their assembly processes. Mitochondria of eukaryotic cells contain a labile copper(I) pool localized in the matrix where also the mitochondrial iron-sulfur (Fe/S) cluster assembly machinery resides to mature mitochondrial Fe/S cluster-containing proteins. Misregulation of copper homeostasis might therefore damage mitochondrial Fe/S protein maturation. To describe, from a molecular perspective, the effects of copper(I) toxicity on such a maturation process, we have here investigated the still unknown mechanism of [4Fe-4S] cluster formation conducted by the mitochondrial ISCA1/ISCA2 and GLRX5 proteins, and defined how copper(I) can impair this process. The molecular model here proposed indicates that the copper(I) and Fe/S protein maturation cellular pathways need to be strictly regulated to avoid copper(I) ion from blocking mitochondrial [4Fe-4S] protein maturation.
authors.affiliation: Department of Pharmacy, University of Naples "Federico II" , Via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Brancaccio
authors.affiliation: Magnetic Resonance Center CERM, University of Florence , Via Luigi Sacconi 6, 50019, Sesto Fiorentino, Florence, Italy.|Department of Chemistry, University of Florence , Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Gallo
authors.affiliation: Magnetic Resonance Center CERM, University of Florence , Via Luigi Sacconi 6, 50019, Sesto Fiorentino, Florence, Italy.|Department of Chemistry, University of Florence , Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Piccioli
authors.affiliation: Department of Pharmacy, University of Naples "Federico II" , Via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.affiliation: Magnetic Resonance Center CERM, University of Florence , Via Luigi Sacconi 6, 50019, Sesto Fiorentino, Florence, Italy.|Department of Chemistry, University of Florence , Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Ciofi-Baffoni
authors.affiliation: Magnetic Resonance Center CERM, University of Florence , Via Luigi Sacconi 6, 50019, Sesto Fiorentino, Florence, Italy.|Department of Chemistry, University of Florence , Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Lucia
authors.identifier: 0000-0003-0562-5774
authors.initials: L
authors.lastname: Banci
mesh_terms: D003300:Copper / Q000737:chemistry / Q000633:toxicity*; D007501:Iron / Q000737:chemistry; D007506:Iron-Sulfur Proteins / Q000737:chemistry; D008928:Mitochondria; D008954:Models, Biological; D013455:Sulfur / Q000737:chemistry
chemical_list: D007506:Iron-Sulfur Proteins; D013455:Sulfur; D003300:Copper; D007501:Iron