Reference Report

Reference
Citation	Clark, I.E., Dodson, M.W., Jiang, C., Cao, J.H., Huh, J.R., Seol, J.H., Yoo, S.J., Hay, B.A., Guo, M. (2006). Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 441(7097): 1162--1166. (Export to RIS)
FlyBase ID	FBrf0193434
Publication Type	Research paper
PubMed ID	16672981
PubMed Abstract	Parkinson's disease is the second most common neurodegenerative disorder and is characterized by the degeneration of dopaminergic neurons in the substantia nigra. Mitochondrial dysfunction has been implicated as an important trigger for Parkinson's disease-like pathogenesis because exposure to environmental mitochondrial toxins leads to Parkinson's disease-like pathology. Recently, multiple genes mediating familial forms of Parkinson's disease have been identified, including PTEN-induced kinase 1 (PINK1; PARK6) and parkin (PARK2), which are also associated with sporadic forms of Parkinson's disease. PINK1 encodes a putative serine/threonine kinase with a mitochondrial targeting sequence. So far, no in vivo studies have been reported for pink1 in any model system. Here we show that removal of Drosophila PINK1 homologue (CG4523; hereafter called pink1) function results in male sterility, apoptotic muscle degeneration, defects in mitochondrial morphology and increased sensitivity to multiple stresses including oxidative stress. Pink1 localizes to mitochondria, and mitochondrial cristae are fragmented in pink1 mutants. Expression of human PINK1 in the Drosophila testes restores male fertility and normal mitochondrial morphology in a portion of pink1 mutants, demonstrating functional conservation between human and Drosophila Pink1. Loss of Drosophila parkin shows phenotypes similar to loss of pink1 function. Notably, overexpression of parkin rescues the male sterility and mitochondrial morphology defects of pink1 mutants, whereas double mutants removing both pink1 and parkin function show muscle phenotypes identical to those observed in either mutant alone. These observations suggest that pink1 and parkin function, at least in part, in the same pathway, with pink1 functioning upstream of parkin. The role of the pink1-parkin pathway in regulating mitochondrial function underscores the importance of mitochondrial dysfunction as a central mechanism of Parkinson's disease pathogenesis.
DOI	10.1038/nature04779
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Nature
Title	Nature
Publication Year	1869-
ISBN/ISSN	0028-0836
Data from Reference
Aberrations (1)
	Df(1)Pink1⁹
Alleles (16)
	CG4095⁹ CG4095^tCa Hsap\PINK1^βTub85D.PC park^Scer\UAS.cGa park^unspecified park^Δ21 park^βTub85D.PC Pink1⁵ Pink1⁹ Pink1^+tCa Pink1^G900 Pink1^Scer\UAS.cCa Pink1^T:Hsap\MYC Pink1^unspecified Pink1^βTub85D.PC Scer\GAL4^how-24B
Constructs (8)
	P{EP} P{Pink1-9myc} P{Pink1^+tCa} P{TMR-hPINK1.C} P{TMR-park.C} P{TMR-Pink1.C} P{UAS-park.G} P{UAS-Pink1.C}
Genes (6)
	CG4095 Hsap\PINK1 park Pink1 Scer\GAL4 Sod2
Insertions (2)
	P{EP}Pink1^G900 P{GawB}how^24B
Natural transposons (1)
	P-element