PINK1 — PTEN Induced Kinase 1

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PINK1 — PTEN Induced Kinase 1

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PINK1 — PTEN Induced Kinase 1

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">PINK1 — PTEN Induced Kinase 1</th>
</tr>
<tr> [@phosphorylation2014]
<td class="label">Symbol</td> [@characterization2010]
<td><strong>PINK1</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>PTEN Induced Kinase 1</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>1p36.12</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/65018" target="_blank">65018</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000158828" target="_blank">ENSG00000158828</a></td>
</tr>
<tr>
<td class="label">OMIM</td>
<td><a href="https://omim.org/entry/608309" target="_blank">608309</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/Q9BXM7" target="_blank">Q9BXM7</a></td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Parkinson's Disease](/diseases/parkinsons-disease)</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Substantia nigra, Cerebral cortex, Mitochondria (widespread)</td>
</tr>
<tr>
<th class="infobox-subheader" colspan="2">Key Mutations</th>
</tr>
<tr>
<td colspan="2" style="font-size:0.85em">Q456X, G309D, W437X, E240K, A168P, L347P, M341I, C-terminal mutations</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ad" style="color:#ef9a9a">AD</

...

PINK1 — PTEN Induced Kinase 1

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">PINK1 — PTEN Induced Kinase 1</th>
</tr>
<tr> [@phosphorylation2014]
<td class="label">Symbol</td> [@characterization2010]
<td><strong>PINK1</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>PTEN Induced Kinase 1</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>1p36.12</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/65018" target="_blank">65018</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000158828" target="_blank">ENSG00000158828</a></td>
</tr>
<tr>
<td class="label">OMIM</td>
<td><a href="https://omim.org/entry/608309" target="_blank">608309</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/Q9BXM7" target="_blank">Q9BXM7</a></td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Parkinson's Disease](/diseases/parkinsons-disease)</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Substantia nigra, Cerebral cortex, Mitochondria (widespread)</td>
</tr>
<tr>
<th class="infobox-subheader" colspan="2">Key Mutations</th>
</tr>
<tr>
<td colspan="2" style="font-size:0.85em">Q456X, G309D, W437X, E240K, A168P, L347P, M341I, C-terminal mutations</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ad" style="color:#ef9a9a">AD</a>, <a href="/wiki/ali" style="color:#ef9a9a">ALI</a>, <a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">2147 edges</a></td>
</tr>
</table>

PINK1 — PTEN Induced Kinase 1

Introduction

Pink1 — Pten Induced Kinase 1 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Pathway / Mechanism Diagram

Mermaid diagram (expand to render)

Overview

PINK1 (PTEN Induced Kinase 1) is a gene located on chromosome 1p36.12 that encodes a serine/threonine-protein kinase crucial for mitochondrial quality control[@hereditary2004]. Pathogenic mutations in PINK1 cause autosomal recessive early-onset Parkinson's Disease, making it one of the most important genes linked to familial PD[@pink2010]. The discovery of PINK1 mutations as a cause of PD in 2004 revealed the critical role of mitochondrial dysfunction in disease pathogenesis.

The protein encoded by PINK1 is [PINK1/proteins), a 581-amino acid kinase that localizes to mitochondria. See the protein page for detailed structural and functional information.

Gene Structure

The PINK1 gene spans approximately 1.5 Mb of genomic DNA on chromosome 1p36.12 and consists of 8 exons[@mitochondrial2012]. The gene produces a single transcript encoding the PINK1 protein kinase.

Regulatory Elements

The PINK1 promoter contains several regulatory elements:

p53 binding sites: PINK1 is a p53 target gene
FOXO3a response elements: Regulated by FOXO3a transcription factor
AMPK response elements: Energy status affects expression
[NF-κB](/entities/nf-kb) sites: Inflammation can modulate expression

Expression is regulated by:

Transcriptional activation: p53, FOXO3a, and AMPK increase expression
Post-transcriptional regulation: Various miRNAs target PINK1 mRNA
Epigenetic modifications: [DNA methylation](/entities/dna-methylation) patterns affect expression

Expression Patterns

In the healthy brain, PINK1 is expressed at high levels in:

Substantia nigra pars compacta: Dopaminergic [neurons](/entities/neurons)
Cerebral [cortex](/brain-regions/cortex): Pyramidal neurons
[Hippocampus](/brain-regions/hippocampus): CA1 and dentate gyrus regions
Cerebellum: Purkinje cells
Peripheral tissues: Heart, skeletal muscle, testis

PINK1 is ubiquitously expressed in all tissues with highest levels in muscle and heart. Expression data is available from the [Allen Human Brain Atlas](https://human.brain-map.org/microarray/search/show?search_term=PINK1).

Normal Physiological Function

PINK1 plays several essential roles in mitochondrial biology:

Mitochondrial quality control: Flags damaged mitochondria for degradation

Mitophagy initiation: Recruits Parkin to dysfunctional mitochondria

Metabolic regulation: Influences mitochondrial respiration and ATP production

Cell survival: Protects against [apoptosis](/mechanisms/apoptosis) and oxidative stress

Mitochondrial dynamics: Regulates fission and fusion processes

Disease Mechanisms

Parkinson's Disease

PINK1 mutations cause autosomal recessive PD through loss of function[@mitochondrial2006]:

Loss of Kinase Activity

Most pathogenic mutations result in:

Reduced or absent kinase activity
Inability to phosphorylate Parkin and other substrates
Failure to initiate mitophagy
Accumulation of damaged mitochondria

Pathogenic Mechanism

The sequence of events in PINK1-linked PD:

Mitochondrial damage occurs (stress, toxins, aging)

PINK1 fails to accumulate on damaged mitochondria

Parkin recruitment is impaired

Mitophagy is blocked

Damaged mitochondria accumulate

Dopaminergic neurons degenerate

Genotype-Phenotype Correlation

PINK1 mutations cause early-onset PD (mean age 30-50 years)
Typical phenotype: Tremor-dominant, good levodopa response
Some patients develop psychiatric symptoms
Disease progression is generally slower than idiopathic PD

Key Mutations

| Mutation | Type | Effect |
|----------|------|--------|
| Q456X | Nonsense | Truncation, loss of kinase domain |
| W437X | Nonsense | Truncation, loss of kinase domain |
| G309D | Missense | Reduced kinase activity |
| E240K | Missense | Impaired substrate binding |
| A168P | Missense | Destabilized protein |
| L347P | Missense | Reduced activity |
| C-terminal mutations | Various | Impaired mitochondrial targeting |

The PINK1-Parkin Pathway

PINK1 and PRKN (Parkin) work together in mitochondrial quality control[@phosphorylation2014]:

Step 1: Mitochondrial Damage

Loss of mitochondrial membrane potential
Import blockade causes PINK1 accumulation

Step 2: PINK1 Activation

PINK1 accumulates on outer mitochondrial membrane
Autophosphorylation activates kinase domain

Step 3: Parkin Recruitment

PINK1 phosphorylates ubiquitin
Phospho-ubiquitin activates Parkin
Parkin is recruited to mitochondria

Step 4: Mitophagy

Parkin ubiquitinates mitochondrial proteins
[Autophagy](/mechanisms/autophagy-lysosome-neurodegeneration) receptors recognize ubiquitinated mitochondria
Mitochondria are engulfed and degraded

Therapeutic Approaches

Kinase Activity Restoration

Kinase activators: Small molecules that enhance PINK1 activity
Stabilizing mutations: Pharmacological chaperones
Protein replacement: Recombinant PINK1 delivery

Mitophagy Enhancement

[mTOR](/entities/mtor) inhibitors: Rapamycin and analogs
AMPK activators: AICAR, metformin
Natural compounds: Urolithin A, resveratrol

Mitochondrial Protection

Antioxidants: CoQ10, MitoQ
Mitochondrial biogenesis inducers: PGC-1α activators

Animal Models

Several models have been developed:

PINK1 knockout mice: Show mitochondrial dysfunction but not neurodegeneration
PINK1 knockdown zebrafish: Display locomotion defects
Drosophila pink1 mutants: Severe mitochondrial defects and neurodegeneration

Research Directions

Current research focuses on:

Developing PINK1 kinase activators
Understanding the full repertoire of PINK1 substrates
Identifying biomarkers for PINK1-linked PD
Elucidating the relationship with sporadic PD

Background

The study of Pink1 — Pten Induced Kinase 1 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

Brain Atlas Resources

[Allen Human Brain Brain Atlas - PINK1 Expression](https://human.brain-map.org/microarray/search/show?search_term=PINK1)
[Allen Cell Type Atlas](https://celltypes.brain-map.org/)
[BrainSpan Transcriptome Atlas](https://brainspan.org/)
[Allen Mouse Brain Atlas](https://mouse.brain-map.org/)

External Links

NCBI Gene: [https://www.ncbi.nlm.nih.gov/gene/65018](https://www.ncbi.nlm.nih.gov/gene/65018)
Ensembl: [https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000158828](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000158828)
OMIM: [https://omim.org/entry/608309](https://omim.org/entry/608309)
UniProt: [https://www.uniprot.org/uniprot/Q9BXM7](https://www.uniprot.org/uniprot/Q9BXM7)
Allen Human Brain Atlas: [PINK1 expression](https://human.brain-map.org/microarray/search/show?search_term=PINK1)
PD Gene: [PINK1 at pdgene.org](https://www.pdgene.org/geneinfo/19)

Allen Brain Atlas Data

Gene Expression

PINK1 (PTEN Induced Kinase 1) expression in brain:

Substantia nigra - Dopaminergic neurons
Hippocampus - Pyramidal neurons
Cerebral cortex - Layer 5 neurons
Heart - High expression (not brain-related)

Single-Cell Expression

PINK1 expressed in:

Dopaminergic neurons
Pyramidal glutamatergic neurons
Cardiac muscle cells (outside brain)

References

[ Valente EM, Abou-Sleiman PM, Caputo V, et al, Hereditary early-onset Parkinson's disease caused by mutations in PINK1 (2004)](https://doi.org/10.1126/science.1096284)

[DOI:10.1371/journal.pbio.1000298](https://doi.org/10.1371/journal.pbio.1000298)

[^3] Greene AW, Grenier K, Aguila MA, et al, Mitochondrial processing peptidase regulates PINK1 processing, import and Parkin recruitment (2012)

[^4] Park J, Lee SB, Son J, et al, Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin (2006)

[^5] Kazlauskaite A, Kondapalli C, Gourlay R, et al, Phosphorylation of Parkin at Serine65 is essential for activation (2014)

[^6] Lin W, Kang UJ, Characterization of PINK1 (PTEN-induced putative kinase 1) stability, localization, and distribution in the brains of aging mice (2010)

[Wang X et al, A potent icaritin derivative ameliorates Parkinson's disease via GPER-mediated mitophagy restoration and dopaminergic neuroprotection (2026)](https://pubmed.ncbi.nlm.nih.gov/41855639/)

[Evola V et al, Gene therapy for Parkinson's disease: current landscape, translational challenges, and future directions (2026)](https://pubmed.ncbi.nlm.nih.gov/41837837/)

[Galla R et al, Neuroprotective Effects of the Combination of Green Tea, Saffron, Docosahexaenoic Acid, and α-Lipoic Acid in an In Vitro Model of Parkinson's Disease (2026)](https://pubmed.ncbi.nlm.nih.gov/41832920/)

[Singh G et al, Miro1 in Parkinson's Disease: A Key Regulator of Mitochondrial Homeostasis and Neurodegeneration (2026)](https://pubmed.ncbi.nlm.nih.gov/41792389/)

Pathway Diagram

The following diagram shows the key molecular relationships involving PINK1 — PTEN Induced Kinase 1 discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

Associated Diseases

Als — associated with

[View disease page](/diseases/als)

ALS — associated with

[View disease page](/diseases/als)

Alzheimer — associated with

[View disease page](/diseases/alzheimer)

Alzheimer disease — associated with

[View disease page](/diseases/alzheimer-disease)

Alzheimer Disease — associated with

[View disease page](/diseases/alzheimer-disease)

Alzheimer's disease — associated with

[View disease page](/diseases/alzheimers-disease)

amyotrophic lateral sclerosis — risk factor for

[View disease page](/diseases/amyotrophic-lateral-sclerosis)

Amyotrophic Lateral Sclerosis — causes

[View disease page](/diseases/amyotrophic-lateral-sclerosis)

dementia — associated with

[View disease page](/diseases/dementia)

Dementia — associated with

[View disease page](/diseases/dementia)

dementia with Lewy bodies — associated with

[View disease page](/diseases/dementia-with-lewy-bodies)

Dementia with Lewy bodies — associated with

[View disease page](/diseases/dementia-with-lewy-bodies)

early-onset Parkinson disease — risk factor for

[View disease page](/diseases/early-onset-parkinson-disease)

Early Onset Parkinson's Disease — risk factor for

[View disease page](/diseases/early-onset-parkinsons-disease)

frontotemporal — associated with

[View disease page](/diseases/frontotemporal)

Lewy body dementia — implicated in

[View disease page](/diseases/lewy-body-dementia)

Parkinson — associated with

[View disease page](/diseases/parkinson)

Parkinson disease — associated with

[View disease page](/diseases/parkinson-disease)

Parkinson Disease — risk factor for

[View disease page](/diseases/parkinson-disease)

Parkinson's disease — associated with