COX2a

COX2a is a nuclear-encoded subunit of the mitochondrial cytochrome c oxidase (Complex IV) in Toxoplasma gondii, where together with COX2B it assembles into the functional complex and supports cyanide-sensitive electron transport (PMID:18036550). Its identity as a Complex IV component is established by co-migration with the complex on Blue Native/2D electrophoresis, mass spectrometry, and immunochemical detection in mitochondria-enriched fractions that exhibit cyanide-sensitive oxygen uptake (PMID:18036550). Beyond its subunit membership and mitochondrial localization, no further mechanistic detail has been characterized in the available corpus.

1. 2007 High

   Whether the apicomplexan COX2a polypeptide is a bona fide component of respiratory Complex IV was unresolved; showing its co-migration with Complex IV in respiring mitochondria established it as a genuine subunit of cytochrome c oxidase.

   Evidence Blue Native/2D electrophoresis, mass spectrometry, and immunochemistry of mitochondria-enriched fractions with cyanide-sensitive oxygen uptake in T. gondii

   PMID:18036550

   Open questions at the time

   • No structural model or stoichiometry of COX2a within Complex IV
   • Functional contribution of COX2a to electron transport not tested by loss-of-function
   • Relationship and assembly relative to COX2B not resolved
2. 2007 Low

   It was unknown whether apicomplexan COX2a precursor maturation resembles that of the split-COX2 chlorophycean algae; a difference in the apparent mass of the mature protein indicated that the mitochondrial targeting sequence is processed differently between the two lineages.

   Evidence SDS-PAGE/immunochemical comparison of mature COX2a molecular mass between T. gondii and Polytomella sp.

   PMID:18036550

   Open questions at the time

   • Single indirect observation (mass difference) without direct mutagenesis or a processing assay
   • Processing site and responsible peptidase not identified
   • Functional consequence of the differential processing unknown

• The functional requirement of COX2a for respiration, its assembly pathway with COX2B, and its structural arrangement within Complex IV remain uncharacterized.
• No genetic loss-of-function or rescue data
• No structural or stoichiometric characterization
• Assembly relationship with COX2B undefined