Characterization of , a Yeast Gene Involved in Copper Metabolism and Assembly of Cytochrome Oxidase

Abstract

Mutations in the COX17 gene of Saccharomyces cerevisiae cause a respiratory deficiency due to a block in the production of a functional cytochrome oxidase complex. Because cox17 mutants are able to express both the mitochondrially and nuclearly encoded subunits of cytochrome oxidase, the Cox17p most likely affects some late posttranslational step of the assembly pathway. A fragment of yeast nuclear DNA capable of complementing the mutation has been cloned by transformation of the cox17 mutant with a library of genomic DNA. Subcloning and sequencing of the COX17 gene revealed that it codes for a cysteine-rich protein with a molecular weight of 8,057. Unlike other previously described accessory factors involved in cytochrome oxidase assembly, all of which are components of mitochondria, Cox17p is a cytoplasmic protein. The cytoplasmic location of Cox17p suggested that it might have a function in delivery of a prosthetic group to the holoenzyme. A requirement of Cox17p in providing the copper prosthetic group of cytochrome oxidase is supported by the finding that a cox17 null mutant is rescued by the addition of copper to the growth medium. Evidence is presented indicating that Cox17p is not involved in general copper metabolism in yeast but rather has a more specific function in the delivery of copper to mitochondria.

Delivering copper within plant cells

“…In yeast and humans, other trafficking pathways deliver copper to super oxide dismutase [34] and to the mitochondria [35]. Given the high degree to which the CCH/RANI pathway is con served among yeast, plants and animals, it is reasonable to assume that plants also contain homologs of the superoxide dismutase and mitochondrial delivery pathways.…”

XIAP: Cell death regulation meets copper homeostasis

“…These subunits require copper as a catalytic co-factor and copper insertion takes place within mitochondria. The copper chaperone Cox17 is one of the factors that plays an important role in the metallation of CcO and its deficiency results in the lack of copper delivery to CcO in yeast [47]. Cox17 is found in both the cytosol and mitochondria.…”

Les bases moléculaires de l’approvisionnement en cuivre

“…En raison de cette rareté, le cuivre intracellulaire est associé à différentes protéines qui le distribuent et l'utilisent ( Figure 2). Trois protéines chaperonnes spécifiques pour chacune de leur cible permettent la distribution du cuivre : Ccs1 [10], Cox17 [11] et Atx1 [12].…”

“…Chez S. cerevisiae, une souche mutante pour COX17 présente une CcO inactive. Le modèle initial suggérait que Cox17 contribuait à l'apport en cuivre à l'intérieur de la mitochondrie [11] bien que l'absence de Cox17 n'affecte pas le niveau de cuivre contenu dans la mitochondrie [21]. De plus, l'environnement réducteur du cytosol laisserait Cox17 sous sa forme réduite, permettant plus facilement son entrée dans l'IMS via le complexe Tom [21].…”