PINK1 is recruited to mitochondria with parkin and associates with LC3 in mitophagy.
Mutations in PTEN-induced putative kinase 1 (PINK1) cause recessive form of Parkinson's disease (PD). PINK1 acts upstream of parkin, regulating mitochondrial integrity and functions. Here, we show that PINK1 in combination with parkin results in the perinuclear mitochondrial aggregation followed by their elimination. This elimination is reduced in cells expressing PINK1 mutants with wild-type parkin. Although wild-type PINK1 localizes in aggregated mitochondria, PINK1 mutants localization remains diffuse and mitochondrial elimination is not observed. This phenomenon is not observed in autophagy-deficient cells. These results suggest that mitophagy controlled by the PINK1/parkin pathway might be associated with PD pathogenesis.
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
Sumihiro
S
Kawajiri
Shinji
S
Saiki
Shigeto
S
Sato
Fumiaki
F
Sato
Taku
T
Hatano
Hiroto
H
Eguchi
Nobutaka
N
Hattori
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002478:Cells, Cultured; D006367:HeLa Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000235:genetics / Q000502:physiology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D000099202:PTEN-Induced Putative Kinase
D008869:Microtubule-Associated Proteins; D046988:Proteasome Endopeptidase Complex; D011494:Protein Kinases; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C477012:MAP1LC3A protein, human; C111567:parkin protein