title: Cox1 mutation abrogates need for Cox23 in cytochromecoxidase biogenesis.
abstract: Cox23 is a known conserved assembly factor for cytochromecoxidase, although its role in cytochromecoxidase (CcO) biogenesis remains unresolved. To gain additional insights into its role, we isolated spontaneous suppressors of the respiratory growth defect incox23∆ yeast cells. We recovered independent colonies that propagated on glycerol/lactate medium forcox23∆ cells at 37°C. We mapped these mutations to the mitochondrial genome and specifically toCOX1yielding 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 ofcox23∆ 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 forcox23∆ cells.
authors.affiliation: University of Utah Health Sciences Center, Departments of Medicine and Biochemistry, Salt Lake City, Utah 84132, USA. ; Present address: Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Dela Cruz
authors.affiliation: University of Utah Health Sciences Center, Departments of Medicine and Biochemistry, Salt Lake City, Utah 84132, USA.
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Jeong
authors.affiliation: University of Utah Health Sciences Center, Departments of Medicine and Biochemistry, Salt Lake City, Utah 84132, USA.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Winge
keywords: COX1; COX23; cytochrome oxidase; mitochondria