The gene PINK1 (phosphatase and tensin homolog (PTEN)-induced kinase 1) encodes a serine/threonine kinase which has been linked with Parkinson’s disease (PD) in 2004 (PMID 27701735). Recessive mutations in several families worldwide that lead to loss-of-function of the PINK1 protein is found to cause early-onset PD and PINK1 is the second commonest cause of autosomal recessive early-onset PD. Single heterozygous PINK1 mutations have been detected in sporadic PD patients and controls with mild or subclinical manifestation of the disease, suggesting that it may represent of susceptibility factor for PD.

PD patients carrying PINK1 mutations show an early disease onset (before 45 years old) characterized by a slow progression and a prolonged beneficial response to L-DOPA.

PINK1 encodes a ubiquitously expressed 63 kDa protein that contains a mitochondrial leader peptide sequence (NLS) at its N-terminal. In healthy cells, full length PINK1 is released from mitochondria and detected in the cytosol where it is maintained at low levels. Conversely, following mitochondria depolarization or damage the full length PINK1 protein accumulates at the outer mitochondrial membrane and acts as a mitochondrial quality control. Evidence indicates that the PINK1 protein can regulate mitochondrial and cytosolic pathways involved in metabolism and cell survival and that its function is highly dependent on its subcellular localization.

The PINK1 protein has a protective role against neuronal death in which mitochondrial dysfunction and deficits in clearance systems are involved.

 

Species PINK1 Mutation Genotype Neurodegeneration (Y/N) Link
Mouse Targeted deletion Deletion of exon 4-7 PINK1-/- N Pink1 null
Mouse Targeted deletion Insertion in exons 2-4 PINK1-/- N mPink1 KO/1
Mouse Targeted deletion Insertion in exons 4-5 PINK1-/- Y/N mPink1 KO/2
Mouse Targeted mutation resulting in deletion G309D mutation by homologus recombination PINK1-/- N Pink1 G309D
Mouse Targeted deletion Triple mutation Pink1, DJ-1 and Parkin PINK1-/- , DJ1-/-, Parkin-/- N Pink1 triple
Rat Targeted deletion ZFN to introduce deletion in exon 4 PINK1-/- Y rPink1 KO

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