COX4

PF3D7_0708700 (COX4) is a component of the mitochondrial respiratory chain Complex IV (cytochrome c oxidase) in Plasmodium falciparum, identified by complexome profiling as part of a complex whose composition is markedly divergent from canonical model organisms, including clade-specific additions (PMID:34155201). The Complex IV to which COX4 belongs is up to 40-fold more prevalent in gametocytes than in asexual blood stages, consistent with an increased reliance on oxidative phosphorylation in the transmissible stage (PMID:34155201). Beyond its assignment as a Complex IV subunit and this stage-dependent abundance pattern, no function, essentiality, or mechanistic role specific to PF3D7_0708700 has been characterized in the available corpus.

1. 2021 Medium

   Whether PF3D7_0708700 participates in the P. falciparum respiratory chain was unknown; complexome profiling assigned it to Complex IV and revealed that this cytochrome c oxidase has a divergent, clade-specific composition and is strongly enriched in gametocytes.

   Evidence Complexome profiling (native PAGE coupled to mass spectrometry) across asexual blood stages and gametocytes of P. falciparum

   PMID:34155201

   Open questions at the time

   • No functional mutagenesis, knockout, or reconstitution establishing the specific role of PF3D7_0708700 within Complex IV
   • The structural placement and interaction partners of PF3D7_0708700 within the divergent complex are not resolved
   • The mechanism driving the gametocyte-specific increase in complex abundance is not addressed

• It remains unknown whether PF3D7_0708700 is individually required for Complex IV assembly or activity, and what molecular contribution it makes distinct from the complex as a whole.
• No gene-specific loss-of-function or biochemical assay for PF3D7_0708700
• No enzymatic activity attributed to PF3D7_0708700 itself