Regulation by mitophagy.
Eukaryotes employ elaborate mitochondrial quality control to maintain the function of the power-generating organelle. Mitochondrial quality control is particularly important for the maintenance of neural and muscular tissues. Mitophagy is specialized version of the autophagy pathway. Mitophagy delivers damaged mitochondria to lysosomes for degradation. Recently, a series of elegant studies have demonstrated that two Parkinson's disease-associated genes PINK1 and parkin are involved in the maintenance of healthy mitochondria as mitophagy. Parkin in co-operation with PINK1 specifically recognizes damaged mitochondria with reduced mitochondrial membrane potential (Δψm), rapidly isolates them from the mitochondrial network and eliminates them through the ubiquitin-proteasome and autophagy pathways. Here we introduce and review recent studies that contribute to understanding the molecular mechanisms of mitophagy such as PINK1 and Parkin-mediated mitochondrial regulation. We also discuss how defects in the PINK1-Parkin pathway may cause neurodegeneration in Parkinson's disease.
Department of Neurology, Juntendo University, Graduate School of Medicine, Tokyo 113-8421, Japan. Electronic address: nhattori@juntendo.ac.jp.
Nobutaka
N
Hattori
Department of Neurology, Juntendo University, Graduate School of Medicine, Tokyo 113-8421, Japan.
Shinji
S
Saiki
Department of Neuroscience for Neurodegenerative Disorders, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
Yuzuru
Y
Imai
D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000235:genetics* / Q000473:pathology; D063306:Mitophagy / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
D011494:Protein Kinases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein
Mitochondrial dysfunction; Mitophagy; PINK1; Parkin; Parkinson’ disease