RRC ID 52873
著者 Cornelissen T, Vilain S, Vints K, Gounko N, Verstreken P, Vandenberghe W.
タイトル Deficiency of parkin and PINK1 impairs age-dependent mitophagy in Drosophila.
ジャーナル Elife
Abstract Mutations in the genes for PINK1 and parkin cause Parkinson's disease. PINK1 and parkin cooperate in the selective autophagic degradation of damaged mitochondria (mitophagy) in cultured cells. However, evidence for their role in mitophagy in vivo is still scarce. Here, we generated a Drosophila model expressing the mitophagy probe mt-Keima. Using live mt-Keima imaging and correlative light and electron microscopy (CLEM), we show that mitophagy occurs in muscle cells and dopaminergic neurons in vivo, even in the absence of exogenous mitochondrial toxins. Mitophagy increases with aging, and this age-dependent rise is abrogated by PINK1 or parkin deficiency. Knockdown of the Drosophila homologues of the deubiquitinases USP15 and, to a lesser extent, USP30, rescues mitophagy in the parkin-deficient flies. These data demonstrate a crucial role for parkin and PINK1 in age-dependent mitophagy in Drosophila in vivo.
巻・号 7
公開日 2018-5-29
DOI 10.7554/eLife.35878
PII 35878
PMID 29809156
PMC PMC6008047
MeSH Aging* Animals Autophagy* Dopaminergic Neurons / metabolism Dopaminergic Neurons / pathology Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / cytology Drosophila melanogaster / metabolism Drosophila melanogaster / physiology* Mitochondria / metabolism Mitochondria / pathology* Mitophagy Muscle, Skeletal / metabolism Muscle, Skeletal / pathology Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism* Ubiquitin-Protein Ligases / genetics Ubiquitin-Protein Ligases / metabolism*
IF 7.08
引用数 30
リソース情報
ショウジョウバエ 3016R-2