Mitochondrial dysfunction is one of the major contributing factors in the pathogenesis of neurodegenerative disorders such as Parkinson’s disease (PD). PINK1 and Parkin are two proteins that are commonly mutated in familial forms of PD known as autosomal-recessive juvenile Parkinsonism (AR-JP). These proteins work together in maintaining mitochondrial health, detecting damaged mitochondria and initiating cascades that lead to their degradation through mitophagy. PINK1/Parkin-mediated mitophagy ensures the removal of toxic mitochondrial products and prevents neuronal loss.

Adapted from Nguyen et al., Trends in Cell Biology 2016 Pubmed
In healthy mitochondria, PINK1 is constitutively processed by mitochondrial proteases, MPP and PARL, resulting in its proteasomal degradation (left panel). In damaged mitochondria, PINK1 accumulates at OMM bound to the TOM complex where it is activated through dimerization and autophosphorylation. Activated PINK1 subsequently phosphorylates ubiquitin resulting in Parkin activation and relocation to the mitochondria where it further ubiquitinates mitochondrial substrates and signals the mitophagy machinery to remove the damaged organelle.
Abbreviations
PINK1-PTEN-induced kinase 1
MPP-Matrix processing peptidase
PARL-Presenilin-associated rhomboid-like protein
TOM-Translocase of the outer membrane
TIM-Translocase of the inner membrane
OMM-Outer mitochondrial membrane
IMM-Inner mitochondrial membrane
BioLegend is proud to offer a variety of antibodies for detection of PD-related proteins including PINK1 and Parkin.

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