PINK1-Parkin Mitophagy Project
Overview
Mitophagy is the selective autophagy of damaged mitochondria. The PINK1-Parkin pathway is the best-characterized mitophagy pathway, where mitochondrial damage stabilizes PINK1 kinase, which recruits and activates the Parkin E3 ubiquitin ligase.
Model Species
Primary: Homo sapiens (human)
- Parkinson's disease relevance
- Well-characterized pathway
Core Pathway Architecture
1. Damage Sensing
- PINK1 - Kinase, stabilized on damaged mitochondria
- TOMM complex - PINK1 import/stabilization
2. Ubiquitin Ligase
- PRKN (Parkin) - E3 ubiquitin ligase
- Phospho-ubiquitin - PINK1 product, Parkin activator
3. Mitophagy Receptors
Ubiquitin-binding autophagy receptors:
- OPTN - Optineurin
- CALCOCO2 (NDP52) - Autophagy receptor
- SQSTM1 (p62) - Autophagy receptor
- TAX1BP1 - Autophagy receptor
- NBR1 - Autophagy receptor
4. Autophagy Machinery
- ULK1 complex - Initiation
- LC3/GABARAP - Autophagosome proteins
- TBK1 - Phosphorylates receptors
5. Alternative Mitophagy
PINK1/Parkin-independent:
- BNIP3/BNIP3L (NIX) - Receptor-mediated
- FUNDC1 - Hypoxia-induced
- PHB2 - Inner membrane receptor
Candidate Genes (~18)
| Gene | UniProt | Function |
|---|---|---|
| PINK1 | Q9BXM7 | Kinase |
| PRKN | O60260 | E3 ligase |
| OPTN | Q96CV9 | Receptor |
| CALCOCO2 | Q13137 | NDP52 receptor |
| SQSTM1 | Q13501 | p62 receptor |
| TAX1BP1 | Q86VP1 | Receptor |
| TBK1 | Q9UHD2 | Kinase |
| BNIP3 | Q12983 | Receptor |
| BNIP3L | O60238 | NIX receptor |
| FUNDC1 | Q8IVP5 | Receptor |
| VCP | P55072 | Extraction |
| MFN2 | O95140 | Parkin substrate |
Disease Relevance
- Parkinson's disease (PINK1, PRKN mutations)
- ALS (OPTN, TBK1 mutations)
- Mitochondrial diseases
Project Status
- [ ] Stub - needs gene folder setup