Table 5.
Mitochondrial Dysfunction in Animal Models of DJ-1-Linked Parkinson's Disease
| Gene/model | Phenotype | Mitochondrial pathology | Mitochondrial activity | Sensitivity to ox. stress and mitochondrial toxins | Reference |
|---|---|---|---|---|---|
| DJ-1 | |||||
| Mouse KO | no major anatomical or neuronal abnormalities, mild motoric deficits, increased striatal DA reuptake, age-dependent up-regulation of antioxidant enzymes | N.D. | normal ATP production, resp. complex activity and Krebs cycle activity;↓aconitase activity;↑ROS production | ↑ sensitivity to ox. stress ↑sensitivity to rotenone, MPTP |
(3, 75) |
| Drosophila KO (DJ-1α/β) | no major abnormalities, locomotor dysfunction, no DAergic neuronal loss | enlarged mitochondria | ↑ ROS production ↑protein oxidation |
↑ sensitivity to ox. stress ↑sensitivity to rotenone, paraquat |
(113, 136) |
| Drosophila RNAi knockdown (DJ-1α) | no major abnormalities; DAergic and photoreceptor neuronal degeneration |
enlarged mitochondria | ↑ ROS production ↑protein oxidation |
↑ sensitivity to ox. stress ↑sensitivity to rotenone, paraquat |
(202) |
| Drosophila KO (DJ-1β) | severe defects in motoric function, no loss of DAergic neurons, extended survival of DAergic neurons | enlarged mitochondria | N.D. | ↑ sensitivity to H2O2 ↓sensitivity to paraquat |
(112, 136) |
MPTP, 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine.