QCR9

QCR9 (PF3D7_0622600) is a subunit of the mitochondrial cytochrome bc1 complex (Complex III) of P. falciparum, identified by complexome profiling as comigrating with other Complex III subunits at ~730 kDa in both asexual blood stages and gametocytes, establishing its physical membership in the complex across life stages (PMID:34155201). Its association with Complex III is further supported by chemoproteomic enrichment with a photoactivatable derivative of the Complex III inhibitor 9-methoxystrobilurin G, in the same study that confirmed 9MG inhibits ubiquinone-cytochrome c reductase activity in P. falciparum extract (PMID:39262389). Beyond its membership in Complex III and its co-behavior with the complex under inhibitor challenge, no QCR9-specific molecular function, structure, or phenotype has been characterized in the available corpus.

1. 2021 Medium

   Whether PF3D7_0622600 belongs to a defined mitochondrial complex was unresolved; complexome profiling placed it physically within Complex III across two life stages, establishing it as a canonical bc1 subunit rather than an unassigned protein.

   Evidence Complexome profiling (blue native PAGE coupled to mass spectrometry) across asexual blood stages and gametocytes

   PMID:34155201

   Open questions at the time

   • Comigration establishes co-assembly but not the specific structural position or contacts of QCR9 within Complex III
   • No functional consequence of QCR9 for complex assembly or activity was tested
   • No direct genetic perturbation of QCR9 was performed
2. 2024 Medium

   It was unknown whether QCR9 co-behaves with Complex III under pharmacological targeting; chemoproteomic enrichment by a Complex III inhibitor derivative, alongside confirmed inhibition of ubiquinone-cytochrome c reductase activity, tied QCR9 to functionally engaged Complex III.

   Evidence Chemoproteomic target profiling with a photoactivatable 9MG derivative plus ubiquinone-cytochrome c reductase activity assay on P. falciparum extract

   PMID:39262389

   Open questions at the time

   • Enrichment does not establish direct binding of the inhibitor to QCR9 specifically rather than to the complex
   • The catalytic subunit targeted is cytochrome b, not QCR9; QCR9's own role in inhibitor action is undefined
3. 2025 Low

   Solvent proteome profiling with atovaquone tested whether QCR9 shows drug-linked thermodynamic behavior consistent with Complex III association, adding orthogonal support for its physical membership.

   Evidence Solvent-induced proteome profiling (SPP) of atovaquone-treated P. falciparum lysates, individual solvent-percentage analysis

   PMID:41308470

   Open questions at the time

   • Stabilisation was significant only at a single solvent concentration and did not reach significance in the primary AUC analysis
   • Single lab and single method; does not demonstrate direct atovaquone binding to QCR9

• The specific molecular contribution of QCR9 to Complex III — its role in complex assembly, stability, or electron transfer, and the phenotypic consequence of its loss — remains unaddressed in the corpus.
• No genetic knockout, knockdown, or rescue of QCR9 reported
• No structural model localizing QCR9 within Complex III
• No QCR9-specific (as opposed to complex-level) biochemical function established