Mitochondrial Pyruvate Carrier Inhibition to Force Metabolic Reprogramming Toward Ketone Utilization
Curated pathway from expert analysis
flowchart TD
A["MPC1/MPC2 Inhibition<br/>Mitochondrial Pyruvate Carrier Blocked"]
B["Glycolytic Shift<br/>Lactate丰度增加"]
C["Astrocyte-Neuron<br/>Lactate Shuttle Enhanced"]
D["Metabolic Reprogramming<br/>Warburg-like State"]
E["Neuronal Energetic<br/>Vulnerability Reduced"]
F["Neurodegeneration<br/>Metabolic Resilience"]
G["MPC Inhibition<br/>as Metabolic Reprogramming Tool"]
A --> B
B --> C
C --> D
D --> E
E --> F
G -.->|"forces"| D
style A fill:#7b1fa2,stroke:#ce93d8,color:#ce93d8
style F fill:#1b5e20,stroke:#a5d6a7,color:#a5d6a7No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for MPC1 yet. Search RCSB →
Median TPM across 13 brain regions for MPC1/MPC2 from GTEx v10.
No clinical trials data linked to this hypothesis yet.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for MPC1.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF C57BL/6J mice on a high‑fat diet receive daily intraperitoneal injections of the MPC inhibitor MSDC‑0160 (10 mg/kg) for 14 days THEN plasma β‑hydroxybutyrate levels will rise by at least 50 % compa | ≥50% increase in plasma β‑hydroxybutyrate (βHB) relative to vehicle‑treated mice. | — no observation — | pending | 0.70 |
| IF primary human hepatocytes cultured in Williams’ E medium supplemented with 1 mM octanoate are treated with 10 µM MSDC‑0160 for 48 h THEN extracellular ketone bodies (acacetate + βHB) increase by ≥2 | ≥2‑fold increase in extracellular ketone bodies; ≥30% reduction in glucose consumption. | — no observation — | pending | 0.60 |