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.


SpeciesPINK1MutationGenotypeNeurodegeneration (Y/N)Link
MouseTargeted deletionDeletion of exon 4-7PINK1-/-NPink1 null
MouseTargeted deletionInsertion in exons 2-4PINK1-/-NmPink1 KO/1
MouseTargeted deletionInsertion in exons 4-5PINK1-/-Y/NmPink1 KO/2
MouseTargeted mutation resulting in deletionG309D mutation by homologus recombinationPINK1-/-NhPink1 G309D
MouseTargeted deletionTriple mutation Pink1, DJ-1 and ParkinPINK1-/- , DJ1-/-, Parkin-/-NPink1 triple
RatTargeted deletionZFN to introduce deletion in exon 4PINK1-/-YrPink1 KO

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