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.
Highlights
Cytochrome c oxidase, the terminal complex of mitochondrial and bacterial respiratory chains [1], makes use of two different types of electron carriers
CCC2 has been shown to code for a cytoplasmic protein of yeast that transfers copper to a membrane-bound ceruloplasmin-like oxidase encoded by FET3 [7, 8]
The respiratory deficiency in C129 is complemented by a o tester strain indicating that the cytochrome oxidase defect is the result of a recessive mutation in a nuclear gene
Summary
Cytochrome c oxidase, the terminal complex of mitochondrial and bacterial respiratory chains [1], makes use of two different types of electron carriers. CCC2 has been shown to code for a cytoplasmic protein of yeast that transfers copper to a membrane-bound ceruloplasmin-like oxidase encoded by FET3 [7, 8]. Even though mutations in CCC2 produce a respiratory defective phenotype, it is not clear whether this is because Ccc2p functions on the pathway of copper transport to mitochondria or whether this is secondary to an iron deficiency. The failure of the mutant to assemble functional cytochrome oxidase is corrected by high concentrations of exogenous copper, indicating that the lesion limits the availability of copper during assembly of the complex. Cox17p is not involved in copper uptake in yeast but rather appears to function in the pathway responsible for copper delivery to mitochondria
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