Inhibition of alternative mitophagy pathways (BNIP3/NIX) in healthy donor cells prevents degradation of transferable mitochondria while maintaining quality control in recipient neurons.
Curated pathway from expert analysis
graph TD
A["Astrocytes / MSCs"] --> B["Healthy Mitochondria Pool"]
B --> C["BNIP3/NIX-Mediated Mitophagy"]
C --> D["Mitochondria Degraded"]
D --> E["Reduced Donor Pool"]
F["PINK1/Parkin-Independent Mitophagy Bypass"] --> G["Selective BNIP3/NIX Inhibition"]
G --> H["Block Alternative Mitophagy in Donors"]
H --> I["Healthy Mito Accumulate"]
I --> J["Enlarged Transferable Mito Pool"]
J --> K["Tunneling Nanotubes"]
J --> L["Extracellular Vesicles"]
K --> M["Mitochondria Delivery to Neurons"]
L --> M
N["Damaged Neurons"] --> O["Bioenergetic Crisis"]
O --> P["ATP Depletion"]
O --> Q["Excessive ROS"]
M --> R["Healthy Mito Integrate into Neurons"]
R --> S["Restored ATP Production"]
R --> T["Normalized ROS Levels"]
R --> U["Ca2+ Homeostasis Recovery"]
S --> V["Neuronal Rescue"]
T --> V
U --> V
V --> W["Neuroprotection Without Parkin Dependency"]
style A fill:#1a3a4a,stroke:#4fc3f7,color:#e0e0e0
style F fill:#264653,stroke:#ffd54f,color:#e0e0e0
style M fill:#1a3a2a,stroke:#81c784,color:#e0e0e0
style W fill:#2a3a1a,stroke:#c5e1a5,color:#e0e0e0



No curated PDB or AlphaFold mapping for BNIP3 yet. Search RCSB →
Median TPM across 13 brain regions for BNIP3/BNIP3L from GTEx v10.
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 BNIP3.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| If hypothesis is true, intervention otherwise be ideal candidates for intercellular transfer | otherwise be ideal candidates for intercellular transfer | — no observation — | pending | 0.50 |
| If hypothesis is true, intervention quantify transfer efficiency using mitochondrial-targeted fluorescent proteins and live-cell imaging | quantify transfer efficiency using mitochondrial-targeted fluorescent proteins and live-cell imaging | — no observation — | pending | 0.50 |
| If hypothesis is true, intervention be optimized for different donor cell types, with particular attention to maintaining cell viability and stemness properties in MSCs | be optimized for different donor cell types, with particular attention to maintaining cell viability and stemness properties in MSCs | — no observation — | pending | 0.50 |
| If hypothesis is true, intervention be stereotactically injected into the substantia nigra to support dopaminergic neurons | be stereotactically injected into the substantia nigra to support dopaminergic neurons | — no observation — | pending | 0.50 |
| If hypothesis is true, intervention provide mitochondrial support to motor neurons | provide mitochondrial support to motor neurons | — no observation — | pending | 0.50 |