The Assembly Factor Pet117 Couples Heme a Synthase Activity to Cytochrome Oxidase Assembly.

Nicholas G Taylor, Samantha Swenson, Nicholas J Harris, Edward M Germany, Jennifer L Fox, Oleh Khalimonchuk

The Journal of biological chemistry 2017 Feb 03

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Heme a is an essential metalloporphyrin cofactor of the mitochondrial respiratory enzyme cytochrome c oxidase (CcO). Its synthesis from heme b requires several enzymes, including the evolutionarily conserved heme a synthase (Cox15). Oligomerization of Cox15 appears to be important for the process of heme a biosynthesis and transfer to maturing CcO. However, the details of this process remain elusive, and the roles of any additional CcO assembly factors that may be involved remain unclear. Here we report the systematic analysis of one such uncharacterized assembly factor, Pet117, and demonstrate in Saccharomyces cerevisiae that this evolutionarily conserved protein is necessary for Cox15 oligomerization and function. Pet117 is shown to reside in the mitochondrial matrix, where it is associated with the inner membrane. Pet117 functions at the later maturation stages of the core CcO subunit Cox1 that precede Cox1 hemylation. Pet117 also physically interacts with Cox15 and specifically mediates the stability of Cox15 oligomeric complexes. This Cox15-Pet117 interaction observed by co-immunoprecipitation persists in the absence of heme a synthase activity, is dependent upon Cox1 synthesis and early maturation steps, and is further dependent upon the presence of the matrix-exposed, unstructured linker region of Cox15 needed for Cox15 oligomerization, suggesting that this region mediates the interaction or that the interaction is lost when Cox15 is unable to oligomerize. Based on these findings, it was concluded that Pet117 mediates coupling of heme a synthesis to the CcO assembly process in eukaryotes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Citation

Nicholas G Taylor, Samantha Swenson, Nicholas J Harris, Edward M Germany, Jennifer L Fox, Oleh Khalimonchuk. The Assembly Factor Pet117 Couples Heme a Synthase Activity to Cytochrome Oxidase Assembly. The Journal of biological chemistry. 2017 Feb 03;292(5):1815-1825