Biochemistry, Department of


Date of this Version



The Journal of Biological Chemistry, VOL. 282, NO. 24, pp. 17442–17449, June 15, 2007


© 2007 by The American Society for Biochemistry and Molecular Biology, Inc.


The hydrogen peroxide sensitivity of cells lacking two proteins,

Sco1 and Cox11, important in the assembly of cytochrome

c oxidase (CcO), is shown to arise from the transient accumulation

of a pro-oxidant heme A-Cox1 stalled intermediate. The

peroxide sensitivity of these cells is abrogated by a reduction in

either Cox1 expression or hemeAformation but exacerbated by

either enhanced Cox1 expression or heme A production arising

from overexpression of COX15. Sco1 and Cox11 are implicated

in the formation of the CuA and CuB sites of CcO, respectively.

The respective wild-type genes suppress the peroxide sensitivities

of sco1∆ and cox11∆ cells, but no cross-complementation is

seen with noncognate genes. Copper-binding mutant alleles of

Sco1 and Cox11 that are nonfunctional in promoting the assembly

of CcO are functional in suppressing the peroxide sensitivity

of their respective null mutants. Likewise, human Sco1 that is

nonfunctional in yeast CcO assembly is able to suppress the peroxide

sensitivity of yeast sco1∆ cells. Thus, a disconnect exists

between the respiratory capacity of cells and hydrogen peroxide

sensitivity. Hydrogen peroxide sensitivity of sco1∆ and cox11

cells is abrogated by overexpression of a novel mitochondrial

ATPase Afg1 that promotes the degradation of CcO mitochondrially

encoded subunits. Studies on the hydrogen peroxide sensitivity

in CcO assembly mutants reveal new aspects of the CcO

assembly process.