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Molecular and Cellular Biology, August 2008, p. 4927-4939, Vol. 28, No. 16
0270-7306/08/$08.00+0     doi:10.1128/MCB.00057-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Coa2 Is an Assembly Factor for Yeast Cytochrome c Oxidase Biogenesis That Facilitates the Maturation of Cox1{triangledown}

Fabien Pierrel,{dagger} Oleh Khalimonchuk, Paul A. Cobine, Megan Bestwick, and Dennis R. Winge*

University of Utah Health Sciences Center, Departments of Medicine and Biochemistry, Salt Lake City, Utah 84132

Received 11 January 2008/ Returned for modification 5 March 2008/ Accepted 28 May 2008

The assembly of cytochrome c oxidase (CcO) in yeast mitochondria is dependent on a new assembly factor designated Coa2. Coa2 was identified from its ability to suppress the respiratory deficiency of coa1{Delta} and shy1{Delta} cells. Coa1 and Shy1 function at an early step in maturation of the Cox1 subunit of CcO. Coa2 functions downstream of the Mss51-Coa1 step in Cox1 maturation and likely concurrent with the Shy1-related heme a3 insertion into Cox1. Coa2 interacts with Shy1. Cells lacking Coa2 show a rapid degradation of newly synthesized Cox1. Rapid Cox1 proteolysis also occurs in shy1{Delta} cells, suggesting that in the absence of Coa2 or Shy1, Cox1 forms an unstable conformer. Overexpression of Cox10 or Cox5a and Cox6 or attenuation of the proteolytic activity of the m-AAA protease partially restores respiration in coa2{Delta} cells. The matrix-localized Coa2 protein may aid in stabilizing an early Cox1 intermediate containing the nuclear subunits Cox5a and Cox6.

* Corresponding author. Mailing address: University of Utah Health Sciences Center, Departments of Medicine and Biochemistry, Salt Lake City, UT 84132. Phone: (801) 585-5103. Fax: (801) 585-3432. E-mail: dennis.winge{at}hsc.utah.edu

{triangledown} Published ahead of print on 9 June 2008.

{dagger} Present address: Laboratoire de Chimie et de Biologie des Métaux, CEA, Grenoble, France.

Molecular and Cellular Biology, August 2008, p. 4927-4939, Vol. 28, No. 16
0270-7306/08/$08.00+0     doi:10.1128/MCB.00057-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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