PINK1 — PTEN Induced Kinase 1 <table class="infobox infobox-gene">
Overview
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PINK1 — PTEN Induced Kinase 1 <table class="infobox infobox-gene">
Overview
Mermaid diagram (expand to render)
SNCA is a human gene. Variants in SNCA have been implicated in Parkinson's Disease (PARK6), Other Associations. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
Gene Symbol: PINK1
Also Known As: PARK6, PTEN-induced putative kinase 1
Gene ID (NCBI): 65018
Chromosomal Location: 1p36.23
Gene Overview PINK1 (PTEN Induced Kinase 1) is a serine/threonine-protein kinase encoded by the PINK1 gene, located on chromosome 1p36.23. It is primarily localized to the outer mitochondrial membrane and plays a critical role in mitochondrial quality control through the activation of parkin-mediated mitophagy [1][2]. Mutations in PINK1 cause autosomal recessive Parkinson's disease (PARK6), making it one of the most common genetic causes of early-onset PD [3].
Protein Structure and Function PINK1 contains:
An N-terminal mitochondrial targeting sequence (MTS)
A serine/threonine kinase domain
A C-terminal regulatory domain
Kinase Activity PINK1 is a mitochondrial serine/threonine-protein kinase that phosphorylates multiple substrates:
Parkin (PRKN): PINK1 phosphorylates parkin at Ser65, activating its E3 ubiquitin ligase activity [4]Ubiquitin: Phosphorylates ubiquitin at Ser65, creating a phospho-ubiquitin signal that amplifies mitophagy [5]Mitochondrial proteins: Including TOM complex subunits and mitochondrial fusion proteinsMitochondrial Quality Control Under normal conditions, PINK1 is imported into mitochondria and degraded. Under mitochondrial stress or damage:
PINK1 accumulates on the outer mitochondrial membrane
It phosphorylates parkin and ubiquitin
Activated parkin ubiquitinates mitochondrial proteins
Damaged mitochondria are targeted for autophagic degradation (mitophagy)
Expression Pattern PINK1 is expressed in:
Brain: Substantia nigra pars compacta (dopaminergic neurons), [hippocampus](/brain-regions/hippocampus), [cortex](/brain-regions/cortex)Peripheral tissues: Heart, skeletal muscle, liver, kidneyCell types: [Neurons](/entities/neurons), [astrocytes](/entities/astrocytes), [microglia](/cell-types/microglia-neuroinflammation)Disease Associations
Parkinson's Disease (PARK6) PINK1 mutations cause autosomal recessive early-onset Parkinson's disease:
Age of onset: 30-50 years
Clinical features: Tremor, bradykinesia, rigidity
Good levodopa response
Often presents with sleep disorders
Other Associations
Alzheimer's disease: Altered PINK1 expression in AD brains [6]Cancer: Tumor suppressor functions reportedMitochondrial disorders: Role in metabolic diseasesTherapeutic Implications
Pharmacological Targets
PINK1 activators: Small molecules to enhance PINK1 kinase activityMitophagy modulators: Compounds that promote mitochondrial clearanceMitochondrial protectors: Prevent mitochondrial dysfunctionResearch Directions
Gene therapy approaches to deliver functional PINK1
Phospho-mimetic parkin activators
Mitochondrial dynamics modulators
[PARK2/parkin](/genes/parkin) - E3 ubiquitin ligase activated by PINK1
[SNCA](/genes/snca) - [Alpha-synuclein](/proteins/alpha-synuclein), Lewy body component
[LRRK2](/genes/lrrk2) - Leucine-rich repeat kinase 2, PD gene
[DJ-1](/genes/park7) - PARK7, PD gene
[MAPT](/genes/mapt) - [Tau protein](/proteins/tau), neurofibrillary tangles
Pathways
[Mitophagy pathway](/mechanisms/mitophagy)
[Mitochondrial dynamics](/mechanisms/mitochondrial-dynamics)
[Ubiquitin-proteasome system](/mechanisms/ubiquitin-proteasome)
[Parkinson's disease pathogenesis](/diseases/parkinsons-disease)
See Also
[SNCA Protein](/proteins/alpha-synuclein)
[Mitophagy pathway](/mechanisms/mitophagy)
[Mitochondrial dynamics](/mechanisms/mitochondrial-dynamics)
[Ubiquitin-proteasome system](/mechanisms/ubiquitin-proteasome)
[Parkinson's disease pathogenesis](/diseases/parkinsons-disease)
External Links
[NCBI Gene: SNCA](https://www.ncbi.nlm.nih.gov/gene/?term=SNCA)
[GeneCards: SNCA](https://www.genecards.org/cgi-bin/carddisp.pl?gene=SNCA)
[OMIM: SNCA](https://omim.org/search?search=SNCA)
[Ensembl: SNCA](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=SNCA)
[Allen Brain Atlas: SNCA](https://human.brain-map.org/microarray/search/show?search_term=SNCA)
References
[Valente et al., PINK1 mutations cause early-onset Parkinson's disease (2004) (2004)](https://doi.org/10.1016/S0140-6736(04)
[Matsuda et al., PINK1 is stabilized by mitochondrial membrane potential (2009) (2009)](https://doi.org/10.1083/jcb.200907029)
[Unknown, Klein & Schlossmacher, PINK1, parkin and mitochondrial dysfunction (2007) (2007)](https://doi.org/10.1002/mds.21325)
[Kondapalli et al., PINK1 is activated by mitochondrial membrane potential (2012) (2012)](https://doi.org/10.1074/jbc.M112.372623)
[Kane et al., PINK1 phosphorylates ubiquitin to activate parkin (2014) (2014)](https://doi.org/10.1083/jcb.201404124)
[Duplan et al., PINK1 activity in neurons (2020) (2020)](https://doi.org/10.3389/fnins.2020.00331)
Pathway Diagram The following diagram shows the key molecular relationships involving PINK1 — PTEN Induced Kinase 1 (PARK6) discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)
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