Cox1 mutation abrogates need for Cox23 in cytochrome c oxidase biogenesis

Authors:

Richard Dela Cruz1,2, Mi-Young Jeong1 and Dennis R. Winge1

doi: 10.15698/mic2016.07.511
Volume 3, pp. 275 to 284, published 30/06/2016.

Affiliations:

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

2 Present address: Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.

Keywords: 

cytochrome oxidase, mitochondria, COX1, COX23.

Corresponding Author(s):

Dennis R. Winge, dennis.winge@hsc.utah.edu

Conflict of interest statement:

None of the authors have a conflict of interest with this reported study.

Please cite this article as:

Richard Dela Cruz, Mi-Young Jeong and Dennis R. Winge (2016). Cox1 mutation abrogates need for Cox23 in cytochrome c oxidase biogenesis. Microbial Cell 3(7): 275-284. doi: 10.15698/mic2016.07.511

© 2016 Dela Cruz et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

Abstract:

Cox23 is a known conserved assembly factor for cytochrome c oxidase, although its role in cytochrome c oxidase (CcO) biogenesis remains unresolved. To gain additional insights into its role, we isolated spontaneous suppressors of the respiratory growth defect in cox23∆ yeast cells. We recovered independent colonies that propagated on glycerol/lactate medium for cox23∆ cells at 37°C. We mapped these mutations to the mitochondrial genome and specifically to COX1 yielding an I101F substitution. The I101F Cox1 allele is a gain-of-function mutation enabling yeast to respire in the absence of Cox23. CcO subunit steady-state levels were restored with the I101F Cox1 suppressor mutation and oxygen consumption and CcO activity were likewise restored. Cells harboring the mitochondrial genome encoding I101F Cox1 were used to delete genes for other CcO assembly factors to test the specificity of the Cox1 mutation as a suppressor of cox23∆ cells. The Cox1 mutant allele fails to support respiratory growth in yeast lacking Cox17, Cox19, Coa1, Coa2, Cox14 or Shy1, demonstrating its specific suppressor activity for cox23∆ cells.