Persistent damaged mitochondria sustain senescence and inflammatory signaling because selective mitochondrial clearance fails.
Curated pathway from expert analysis
flowchart TD
A["Mitochondrial Membrane Potential Loss<br/>Damaged Organelle Signal"]
B["PINK1 Kinase Stabilization<br/>Outer Membrane Accumulation"]
C["Parkin / PRKN Recruitment<br/>E3 Ubiquitin Ligase Activation"]
D["Ubiquitin-Tagged Outer Membrane<br/>p62 / NDP52 / OPTN Adapters"]
E["Autophagosome Engulfment<br/>LC3-II Conjugation"]
F["Lysosomal Degradation<br/>Mitochondrial Clearance"]
G["PINK1 Loss-of-Function<br/>Mitophagy Collapse"]
A --> B
B --> C
C --> D
D --> E
E --> F
G -.->|"blocks"| B
style A fill:#7b1fa2,stroke:#ce93d8,color:#ce93d8
style F fill:#1b5e20,stroke:#81c784,color:#81c784
style G fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9aNo linked papers recorded for this hypothesis yet.
Median TPM across 13 brain regions for PINK1 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 PINK1.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF primary mouse embryonic fibroblasts (MEFs) are subjected to 10 Gy gamma-irradiation, THEN PINK1-knockout cells will accumulate ≥50% more mitochondrial ROS (MitoSOX Red+) and ≥40% higher mitochondri | PINK1-KO MEFs show significantly elevated mitochondrial dysfunction markers (ROS accumulation, hyperpolarization) compared to irradiated WT controls, indicating | — no observation — | pending | 0.65 |
| IF 8-week-old C57BL/6 mice receive focal 30 Gy X-ray irradiation to the left cortex AND are treated with AAV9-PINK1 expression vector intracranially 24h prior, THEN AAV-PINK1-treated mice will exhibit | PINK1 overexpression mitigates radiation-induced senescence and neuroinflammation, confirming PINK1-PRKN mitophagy as the rate-limiting lesion. | — no observation — | pending | 0.55 |