Abstract:
:Mitochondrial dysfunction is an early sign of many neurodegenerative diseases. Very recently, two Parkinson disease (PD) associated genes, PINK1 and Parkin, were shown to mediate the degradation of damaged mitochondria via selective autophagy (mitophagy). PINK1 kinase activity is needed for prompt and efficient Parkin recruitment to impaired mitochondria. PD-associated Parkin mutations interfere with the process of mitophagy at distinct steps. Here we show that whole mitochondria are turned over via macroautophagy. Moreover, disease-associated PINK1 mutations also compromise the selective degradation of depolarized mitochondria. This may be due to the decreased physical binding activity of PD-linked PINK1 mutations to Parkin. Thus, PINK1 mutations abrogate autophagy of impaired mitochondria upstream of Parkin. In addition to compromised PINK1 kinase activity, reduced binding of PINK1 to Parkin leads to failure in Parkin mitochondrial translocation, resulting in the accumulation of damaged mitochondria, which may contribute to disease pathogenesis.
journal_name
Autophagyjournal_title
Autophagyauthors
Geisler S,Holmström KM,Treis A,Skujat D,Weber SS,Fiesel FC,Kahle PJ,Springer Wdoi
10.4161/auto.6.7.13286subject
Has Abstractpub_date
2010-10-01 00:00:00pages
871-8issue
7eissn
1554-8627issn
1554-8635pii
13286journal_volume
6pub_type
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