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.

[4Fe-4S] Cluster Assembly in Mitochondria and Its Impairment by Copper / Brancaccio, Diego; Gallo, Angelo; Piccioli, Mario; Novellino, Ettore; Ciofi-Baffoni, Simone; Banci, Lucia. - In: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. - ISSN 0002-7863. - STAMPA. - 139:(2017), pp. 719-730. [10.1021/jacs.6b09567]

[4Fe-4S] Cluster Assembly in Mitochondria and Its Impairment by Copper

PICCIOLI, MARIO;CIOFI BAFFONI, SIMONE;BANCI, LUCIA
2017

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.
139
719
730
Brancaccio, Diego; Gallo, Angelo; Piccioli, Mario; Novellino, Ettore; Ciofi-Baffoni, Simone; Banci, Lucia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2158/1083352
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