| 31607 | Q0KHV6 | PINK1_DROME | Serine/threonine-protein kinase Pink1, mitochondrial (EC 2.7.11.1) (PTEN-induced putative kinase 1) | DISRUPTION PHENOTYPE | Adults display various phenotypes that appear to be the result of mitochondrial abnormalities and/or mitochondrial dysfunction (PubMed:16672980, PubMed:16672981, PubMed:18799731, PubMed:18443288, PubMed:24901221, PubMed:27906179, PubMed:30772175). In various tissues including the indirect flight muscles (IFM), thoracic muscles, sperm, cardiomyocytes and neurons including 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:16672980, PubMed:16672981, PubMed:18443288, PubMed:18799731, PubMed:24901221, PubMed:27906179, PubMed:23509287). As a result adults are reduced in size, display reduced survival and decreased fertility (PubMed:16672980, PubMed:16672981, PubMed:18799731). They also exhibit age-dependent and progressive degradation of the IFM and 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:16672980, PubMed:18443288, PubMed:24901221, PubMed:27906179). Also affects non-motor behaviors such as reduced learning, intermediate-term memory and irregular circadian rhythms under constant darkness, likely as a result of the neurodegradation (PubMed:28435104). On the surface of mitochondria enriched with a deleterious mutation, negative regulation of larp-mediated protein synthesis is reduced, and as a consequence the transmission of the deleterious mtDNA mutation to the mature oocyte is more random compared to control oocytes which display decreased inheritance of the mutation (PubMed:30772175). RNAi-mediated knockdown increases the net velocity of anterograde mitochondrial transport in motor neurons, whereas retrograde transport is largely unaffected (PubMed:22396657). 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 knockout of Pink1 and Drp1 severely disrupts mitochondrial fusion resulting in mitochondrial aggregates and long threads of mitochondrial tubules (PubMed:18443288). Double knockdown with Paris, improves climbing performance defects and rescues decreased mRNA levels of srl, ewg and TFAM, observed in Pink1 mutants (PubMed:32138754). {ECO:0000269|PubMed:16672980, ECO:0000269|PubMed:16672981, ECO:0000269|PubMed:18443288, ECO:0000269|PubMed:18799731, ECO:0000269|PubMed:22396657, ECO:0000269|PubMed:23509287, ECO:0000269|PubMed:24901221, ECO:0000269|PubMed:27906179, ECO:0000269|PubMed:28435104, ECO:0000269|PubMed:30772175, ECO:0000269|PubMed:32138754}. |