Affinage · Toxoplasma gondii

MPC1

mitochondrial pyruvate carrier protein 1 · UniProt A0A125YT77

Annotated
2026-09-08
1 papers in source corpus 1 papers cited in narrative 3 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

In Toxoplasma gondii, MPC1 is a subunit of the mitochondrial pyruvate carrier that couples cytosolic glycolysis to the mitochondrial TCA cycle by importing pyruvate into the mitochondrion (PMID:36920199). MPC1 assembles with MPC2 into a heteromeric carrier complex whose transport function is conserved, as both subunits restore growth on leucine and valine in a transport-deficient yeast mutant (PMID:36920199). Genetic ablation of MPC1 impairs the synthesis of acetyl-CoA from glucose and reduces carbon flux through glycolysis and the TCA cycle, phenocopying loss of branched-chain ketoacid dehydrogenase and thereby placing the carrier at the junction between cytosolic and mitochondrial carbon metabolism, with a corresponding reduction in asexual parasite growth (PMID:36920199). Despite this metabolic role, MPC1 disruption has only a modest effect on virulence in mice, indicating that the parasite compensates for loss of cytosolic pyruvate import through broader metabolic plasticity (PMID:36920199). Beyond these findings, no structural model or in vitro reconstitution of the carrier has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 2023 Medium

    Establishing whether T. gondii possesses a functional pyruvate transporter answered how the parasite might move glycolytic pyruvate into the mitochondrion, identifying MPC1/MPC2 as a conserved carrier complex.

    Evidence Yeast complementation assay and genetic identification of complex subunits in T. gondii

    PMID:36920199

    Open questions at the time
    • No in vitro reconstitution demonstrating direct pyruvate transport
    • No structural model of the MPC1/MPC2 complex
    • Stoichiometry and assembly of the complex not resolved
  2. 2023 High

    Determining the metabolic consequence of losing the carrier answered where MPC sits in central carbon metabolism, showing it links cytosolic glycolysis to the mitochondrial TCA cycle via acetyl-CoA generation.

    Evidence Conditional/genetic knockout with 13C glucose isotopic flux labeling, growth assays, and epistatic comparison to a BCKDH mutant

    PMID:36920199

    Open questions at the time
    • Alternative pyruvate/carbon sources compensating in the knockout not fully mapped
    • Direct measurement of pyruvate import rate not performed
    • Single-lab evidence
  3. 2023 Medium

    Testing MPC1 requirement in vivo answered whether cytosolic pyruvate import is essential for pathogenesis, revealing it is dispensable for virulence and pointing to metabolic redundancy.

    Evidence Mouse infection model comparing MPC1 knockout parasites to wild type

    PMID:36920199

    Open questions at the time
    • Compensating pathways sustaining virulence not identified
    • Single method, single lab
    • No assessment across life-cycle stages

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular basis of pyruvate transport by the MPC1/MPC2 complex and the identity of the compensatory pathways sustaining growth and virulence in its absence remain unresolved.
  • No structural or biochemical reconstitution of transport
  • Compensatory carbon-source pathways uncharacterized
  • Regulation of carrier expression/activity unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
MPC2
Complex memberships
Mitochondrial pyruvate carrier (MPC) complex (MPC1/MPC2)

Evidence

Reading pass · 3 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2023 MPC1 forms a conserved mitochondrial pyruvate carrier (MPC) complex together with MPC2 in T. gondii, and the two subunits functionally complement a yeast mutant deficient in growth on leucine and valine, establishing their conserved role as pyruvate transporters. Yeast complementation assay, genetic identification of complex subunits Microbiology spectrum Medium 36920199
2023 Genetic ablation of MPC1 (alone or together with MPC2) reduces parasite growth and impairs synthesis of acetyl-CoA from glucose, demonstrated by isotopic labeling, correlating with decreased carbon flux through glycolysis and the TCA cycle; the phenotype mimics deletion of branched-chain ketoacid dehydrogenase (BCKDH), placing MPC at the link between cytosolic glycolysis and mitochondrial TCA cycle. Conditional/genetic knockout, isotopic glucose metabolic labeling (13C flux analysis), growth assays Microbiology spectrum High 36920199
2023 Disruption of MPC1 exerts only a modest effect on parasite virulence in mice, indicating that the mitochondrion can compensate for loss of cytosolic pyruvate import, consistent with metabolic plasticity. Mouse infection model with MPC1 knockout parasites Microbiology spectrum Medium 36920199

Source papers

Stage 0 corpus · 1 paper · ranked by NIH iCite citations
Year Title Journal Citations PMID
2023 The Mitochondrial Pyruvate Carrier Coupling Glycolysis and the Tricarboxylic Acid Cycle Is Required for the Asexual Reproduction of Toxoplasma gondii. Microbiology spectrum 13 36920199