| 40336 |
Q7KTX7 |
PRKN_DROME |
E3 ubiquitin-protein ligase parkin (EC 2.3.2.31) |
DISRUPTION PHENOTYPE |
Pupal lethal; large percentage fail to enclose (PubMed:15073152). Escapers that develop into adults display various phenotypes that appear to be the result of mitochondrial abnormalities and/or mitochondrial dysfunction (PubMed:16672980, PubMed:24192653, PubMed:23509287, PubMed:29497364). In various tissues including the indirect flight muscles (IFM), thoracic muscles, sperm, cardiomyocytes and neurons such as the dopaminergic (DA) neurons, mitochondria display abnormalities such as swelling, loss of cristae, fragmentation, aggregation and/or mitochondrial disorganization, and they are dysfunctional resulting in defects such as mitochondrial depolarization, increased reactive oxygen species (ROS) production, reduced ATP, decreased mitochondrial DNA and reduced mitochondrial protein levels (PubMed:15073152, PubMed:17123504, PubMed:18957282, PubMed:18799731, PubMed:20483372, PubMed:24192653, PubMed:24901221, PubMed:29497364). As a result adults are reduced in size, display reduced survival and decreased fertility (PubMed:15073152, PubMed:16672980, PubMed:17123504, PubMed:24192653, PubMed:24901221, PubMed:29497364). They also exhibit age-dependent and progressive degradation of the IFM and the DA neurons, especially in the protocerebral posterior lateral 1 (PPL1) cluster, which likely contribute to the observed locomotive defects, down-turned rigid wings and crushed thorax phenotypes (PubMed:15073152, PubMed:16002472, PubMed:18957282, PubMed:18799731, PubMed:24901221, PubMed:29497364). However, another report did not observe any age-dependent dopaminergic neuron loss within 21 days post-eclosion (PubMed:15073152). Also affects non-motor behaviors such as reduced three-hour memory performance and irregular circadian rhythms under constant darkness, likely as a result of the neurodegradation (PubMed:28435104). Double knockout of Pink1 and park display no increase in the severity of their phenotypes compared to single mutants (PubMed:16672980). However, expression of park in Pink1 mutants markedly rescues most of the Pink1 mutant phenotypes, whereas expression of Pink1 in park mutants fails to rescue the defective thorax and abnormal wing position (PubMed:16672980). Double knockdown with Paris, improves climbing performance defects and rescues decreased mRNA levels of srl, ewg and TFAM, observed in park mutants (PubMed:32138754). {ECO:0000269|PubMed:15073152, ECO:0000269|PubMed:16002472, ECO:0000269|PubMed:16672980, ECO:0000269|PubMed:17123504, ECO:0000269|PubMed:18799731, ECO:0000269|PubMed:18957282, ECO:0000269|PubMed:20483372, ECO:0000269|PubMed:23509287, ECO:0000269|PubMed:24192653, ECO:0000269|PubMed:24901221, ECO:0000269|PubMed:28435104, ECO:0000269|PubMed:29497364, ECO:0000269|PubMed:32138754}. |