PINK1-dependent recruitment of Parkin to mitochondria in mitophagy

Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) and PARK2/Parkin mutations cause autosomal recessive forms of Parkinson's disease. Upon a loss of mitochondrial membrane potential (DeltaPsi(m)) in human cells, cytosolic Parkin has been reported to be recruited to mitochondria, which is followed by a stimulation of mitochondrial autophagy. Here, we show that the relocation of Parkin to mitochondria induced by a collapse of DeltaPsi(m) relies on PINK1 expression and that overexpression of WT but not of mutated PINK1 causes Parkin translocation to mitochondria, even in cells with normal DeltaPsi(m). We also show that once at the mitochondria, Parkin is in close proximity to PINK1, but we…

• UD
  U.S. Department of Defense

  Awards: W81XWH-08-1-0522, W81XWH, DAMD 17-03-1, W81XWH-08-1-0465
• MD
  Muscular Dystrophy Association
• NI
  National Institutes of Health

  Awards: NS064191, NS38377, NS042269, W81XWH, NS38370, W81XWH-08-1-0465, W81XWH-08-1-0522