The heme a molecule is an obligatory cofactor in the terminal enzyme complex of the electron transport chain, cytochrome c oxidase. Heme a is synthesized from heme o by a multi-spanning inner membrane protein, heme a synthase (Cox15 in the yeast Saccharomyces cerevisiae). The insertion of heme a is critical for cytochrome c oxidase function and assembly, but this process has not been fully elucidated. To improve our understanding of heme a insertion into cytochrome c oxidase, here we investigated the protein-protein interactions that involve Cox15 in S. cerevisiae In addition to observing Cox15 in homooligomeric complexes, we found that a portion of Cox15 also associates with the mitochondrial respiratory supercomplexes. When supercomplex formation was abolished, as in the case of stalled cytochrome bc₁ or cytochrome c oxidase assembly, Cox15 maintained an interaction with select proteins from both respiratory complexes. In the case of stalled cytochrome bc₁ assembly, Cox15 interacted with the late-assembling cytochrome c oxidase subunit, Cox13. When cytochrome c oxidase assembly was stalled, Cox15 unexpectedly maintained its interaction with the cytochrome bc₁ protein, Cor1. Our results indicate that Cox15 and Cor1 continue to interact in the cytochrome bc₁ dimer even in the absence of supercomplexes or when the supercomplexes are destabilized. These findings reveal that Cox15 not only associates with respiratory supercomplexes, but also interacts with the cytochrome bc₁ dimer even in the absence of cytochrome c oxidase.

• PMID: 30181213
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Reference Type

Journal Article | Research Support, N.I.H., Extramural

Authors

Herwaldt EJ, Rivett ED, White AJ, Hegg EL

Primary Lit For

COR1 | QCR8 | COX4 | COX13 | RCF1 | COX5A | COX15 | RCF2

Additional Lit For

Mitochondrial respiratory chain complex IV, COX5A variant

Review For