PTEN-induced putative kinase 1 (PINK1) is a serine/threonine kinase with important functions in mitochondrial quality control. Together with the Parkin protein, PINK1 is able to regulate the selective degradation of damaged mitochondria through autophagy. Normally PINK1 is imported into the mitochondria where it is targeted for proteolytic cleavage. This cleavage event results in unstable products and is the reason PINK1 is difficult to detect in healthy mitochondria. In damaged mitochondria loss of the membrane potential prevents the import of PINK1 and causes it to reside in the outer mitochondrial membrane. Exposed PINK1 in the outer membrane then recruits Parkin which acts as an E3 ligase to ubiquitinate mitochondrial proteins. This leads to mitochondrial degradation through either proteasome or autophagy pathways and can protect cells from oxidative stress induced apoptosis. PINK1 may also regulate mitochondrial fission/fusion events. Mutations in PINK1, especially in the kinase domain, are linked to Parkinson’s disease.
Lutz et al. used the PINK1 antibody to study the role of PINK1/Parkin in mitochondrial fragmentation (1). The group confirmed siRNA knockdown of PINK1 through western blotting and identified the resulting mitochondrial morphology defects. Similarly the Haass group also used the PINK1 antibody to confirm knockdown of protein levels (2). Their study showed wild-type PINK1 but not PINK1 with Parkinson’s causing mutations was able to rescue mitochondrial defects. For both studies the PINK1 antibody was an invaluable tool to follow PINK1 levels and together they demonstrated the role of PINK1 in mitochondrial morphology and its link to Parkinson’s disease. A recent publication by Bifsha et al. used the PINK1 antibody for immunofluorescence to identify Rgs6 as an important player in Parkinson’s disease (3). Rgs6 null mice had a substantial increase in PINK1 protein in degenerating dopaminergic neurons. The Przedborski group at Columbia University used the PINK1 antibody to examine the topology of PINK1 in the mitochondrial membrane (4). Through western blotting and cell fractionation experiments the group demonstrated that the PINK1 kinase domain faces the cytoplasm while the N-terminal tail resides inside the mitochondria.
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