QCR8

QCR8 (PF3D7_0306000) is a subunit of the cytochrome bc1 respiratory chain Complex III in the Plasmodium falciparum mitochondrion, assigned by complexome profiling of native mitochondrial complexes, which also revealed a composition divergent from traditional model organisms and up to 40-fold higher abundance of respiratory chain components in gametocytes relative to asexual blood stages (PMID:34155201). Its physical membership in this complex is independently supported by solvent proteome profiling, in which QCR8 is significantly stabilized upon treatment of parasite lysates with the Complex III inhibitor atovaquone (PMID:41308470). Beyond its assignment as a Complex III subunit and this stage-dependent enrichment, no specific molecular function of QCR8 within the complex has been characterized in the available corpus.

1. 2021 Medium

   Whether PF3D7_0306000 belongs to a defined mitochondrial complex was unknown; systematic native-complex mapping established it as a subunit of the cytochrome bc1 Complex III and revealed marked up-regulation of the respiratory chain in gametocytes.

   Evidence Complexome profiling by co-fractionation and mass spectrometry across asexual blood stages and gametocytes

   PMID:34155201

   Open questions at the time

   • Does not define the specific structural or catalytic role of QCR8 within Complex III
   • Does not establish whether QCR8 is essential for complex assembly or activity
   • Functional consequence of gametocyte-stage enrichment not tested
2. 2025 Medium

   Whether the complexome assignment reflected genuine, drug-relevant physical association was unresolved; ligand-induced stability profiling confirmed QCR8 is stabilized by the Complex III inhibitor atovaquone, corroborating its membership in the atovaquone-targeted complex.

   Evidence Solvent proteome profiling (SPP) of atovaquone-treated P. falciparum lysates detected by mass spectrometry

   PMID:41308470

   Open questions at the time

   • Does not show QCR8 directly binds atovaquone versus stabilization via the complex
   • Does not establish QCR8's contribution to atovaquone sensitivity or resistance
   • No reconstitution or subunit-level functional assay

• The specific molecular function of QCR8 within Complex III, its requirement for complex assembly or electron transfer, and the significance of its gametocyte enrichment remain uncharacterized in the available corpus.
• No genetic knockout or knockdown of QCR8 reported
• No structural model of QCR8 within the P. falciparum Complex III
• No defined molecular activity beyond complex membership