한빛사논문, 상위피인용논문
Abstract
Jeehye Park1,2,6, Sung Bae Lee1,2,6, Sungkyu Lee1,2, Yongsung Kim1,2, Saera Song1,2, Sunhong Kim1,2, Eunkyung Bae3, Jaeseob Kim2,3, Minho Shong4, Jin-Man Kim5 and Jongkyeong Chung1,2
Autosomal recessive juvenile parkinsonism (AR-JP) is an early-onset form of Parkinson''s disease characterized by motor disturbances and dopaminergic neurodegeneration1, 2. To address its underlying molecular pathogenesis, we generated and characterized loss-of-function mutants of Drosophila PTEN-induced putative kinase 1 (PINK1)3, a novel AR-JP-linked gene4. Here, we show that PINK1 mutants exhibit indirect flight muscle and dopaminergic neuronal degeneration accompanied by locomotive defects. Furthermore, transmission electron microscopy analysis and a rescue experiment with Drosophila Bcl-2 demonstrated that mitochondrial dysfunction accounts for the degenerative changes in all phenotypes of PINK1 mutants. Notably, we also found that PINK1 mutants share marked phenotypic similarities with parkin mutants. Transgenic expression of Parkin markedly ameliorated all PINK1 loss-of-function phenotypes, but not vice versa, suggesting that Parkin functions downstream of PINK1. Taken together, our genetic evidence clearly establishes that Parkin and PINK1 act in a common pathway in maintaining mitochondrial integrity and function in both muscles and dopaminergic neurons.
Correspondence to: Jongkyeong Chung1,2 Correspondence and requests for materials should be addressed to J.C.
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