Table 4.
Mitochondrial Dysfunction in Animal Models of Parkin-Linked Parkinson's Disease
| Gene/model | Phenotype | Mitochondrial pathology | Mitochondrial activity | Sensitivity to ox. stress and mitochondrial toxins | Reference |
|---|---|---|---|---|---|
| PARKIN | |||||
| Mouse KO | No major abnormalities,↓body weight | No major abnormalities, decreased level of mitochondrial proteins | ↓ activity in resp. complex I and IV ↑ROS production ↑protein oxidation |
↑ sensitivity to ox. stress ↑sensitivity to rotenone |
(133, 151, 179) |
| Drosophila KO | Male sterility,↓lifespan, DAergic neuronal degeneration | Swollen mitochondria, disintegration of cristae | ↓ activity in resp. complex | ↑ sensitivity to ox. stress ↑sensitivity to rotenone |
(61, 140) |
| Leukocytes (PD patients, hom. deletion of exons 4–8; het. C1032T) | N.D. | N.D. | ↓ activity in resp. complex | N.D. | (123) |
| Fibroblasts (PD patients, homozygous mutations) | N.D. | Greater degree of mitochondrial branching | ↓ ΔΨ ↓ATP production ↓activity in respiratory complex I |
↑ sensitivity to rotenone | (122) |
| PINK1/PARKIN | |||||
| Drosophila double KO | similar to PINK1 and parkin single mutants | Similar to PINK1 and parkin single mutants | N.D. | N.D. | (22) |
DA neurons, dopaminergic neurons; het., heterozygous; hom., homozygous; PD, Parkinson's disease.