PINK1

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PINK1

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PINK1

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">PINK1</th>
</tr>
<tr>
<td class="label">Gene</td>
<td>[PINK1](/genes/pink1)</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">PDB</td>
<td><a href="https://www.rcsb.org/structure/6EQI" target="_blank">6EQI</a>, <a href="https://www.rcsb.org/structure/7JZZ" target="_blank">7JZZ</a></td>
</tr>
<tr>
<td class="label">Mol. Weight</td>
<td>63 kDa (full-length), 52 kDa (processed)</td>
</tr>
<tr>
<td class="label">Localization</td>
<td>Mitochondrial outer membrane</td>
</tr>
<tr>
<td class="label">Family</td>
<td>Serine/threonine kinase family</td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Parkinson's Disease](/diseases/parkinsons-disease)</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

Overview

...

PINK1

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">PINK1</th>
</tr>
<tr>
<td class="label">Gene</td>
<td>[PINK1](/genes/pink1)</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">PDB</td>
<td><a href="https://www.rcsb.org/structure/6EQI" target="_blank">6EQI</a>, <a href="https://www.rcsb.org/structure/7JZZ" target="_blank">7JZZ</a></td>
</tr>
<tr>
<td class="label">Mol. Weight</td>
<td>63 kDa (full-length), 52 kDa (processed)</td>
</tr>
<tr>
<td class="label">Localization</td>
<td>Mitochondrial outer membrane</td>
</tr>
<tr>
<td class="label">Family</td>
<td>Serine/threonine kinase family</td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Parkinson's Disease](/diseases/parkinsons-disease)</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

Overview

PINK1 (PTEN-induced kinase 1) is a mitochondrial serine/threonine-protein kinase encoded by the [PINK1](/proteins/pink1-protein) gene [@zheng2021]. It plays a critical role in mitochondrial quality control through the initiation of mitophagy, the selective [autophagy](/entities/autophagy) of damaged mitochondria [@khan2020]. PINK1 is one of the most important genes linked to early-onset Parkinson's disease (PD), with recessive loss-of-function mutations causing familial PD [@georgakopoulos2017].

PINK1 was first identified as a gene upregulated by PTEN tumor suppressor, hence its name "PTEN-induced kinase 1" [@dodson2014]. It is highly expressed in [neurons](/entities/neurons), particularly in the substantia nigra, and its dysfunction leads to mitochondrial impairment and dopaminergic neuron degeneration [@pagan2019].

Structure

PINK1 contains several functional domains:

Mermaid diagram (expand to render)

N-terminal mitochondrial targeting sequence (MTS): Directs PINK1 to mitochondria [@clark2006]
Transmembrane domain: Anchors PINK1 to the mitochondrial outer membrane [@valek2021]
Kinase domain (C-terminal): Serine/threonine-protein kinase activity [^8]
Ubiquitin-like domain: Binds ubiquitin and parkin [^9]

PINK1-Parkin Mitophagy Pathway

Mermaid diagram (expand to render)

Quality Control Mechanism

Healthy mitochondria: PINK1 is imported and degraded [^10]

Mitochondrial damage: Loss of membrane potential prevents import [^11]

PINK1 accumulation: Stabilizes on outer membrane [^12]

Parkin recruitment: Phosphorylates parkin and ubiquitin [^13][^14]

Mitophagy initiation: Triggers selective autophagy

See also: [PINK1/Parkin Mitophagy Pathway](/mechanisms/pink1-parkin-mitophagy-pathway).

Normal Function

Mitochondrial Quality Control

Mitophagy initiation: Master regulator of damaged mitochondria clearance
Mitochondrial dynamics: Regulates fission and fusion [^15][^16]
Mitochondrial trafficking: Controls neuronal transport [^17]

Metabolic Regulation

Energy metabolism: Affects ATP production [^18]
Oxidative stress response: Activates antioxidant pathways [^19]
Calcium homeostasis: Regulates mitochondrial calcium handling [^20]
Anti-apoptotic function: Inhibits mitochondrial [apoptosis](/mechanisms/apoptosis) pathway [^21]

Parkinson's Disease

Genetic Link

PINK1 mutations cause autosomal recessive juvenile Parkinson's disease (PARK6) [^22]:

Prevalence: ~1-9% of familial PD cases [^23]
Age of onset: Typically 30-50 years (younger than sporadic PD) [^24]
Clinical features: Tremor, bradykinesia, rigidity; good levodopa response [^25]
Neuropathology: Loss of dopaminergic neurons in substantia nigra [^26]

Pathogenic Mechanisms

PINK1 dysfunction leads to PD through several mechanisms [^27]:

Failed mitophagy: Accumulation of damaged mitochondria [^28]
Oxidative stress: Increased [ROS](/entities/reactive-oxygen-species) production [^29]
Energy deficit: Impaired ATP production [^30]
Dopaminergic neuron vulnerability: Specific susceptibility of dopaminergic neurons [^31]

Therapeutic Implications

Pharmacological Strategies

Multiple therapeutic approaches target PINK1 [^32]:

Kinase activators: Small molecules that enhance PINK1 activity [^33]
Mitophagy enhancers: Compounds that promote PINK1-Parkin pathway [^34]
Mitochondrial protectors: Antioxidants and mitochondrial stabilizers [^35]

See also: [PINK1/Parkin Activators](/therapeutics/pink1-parkin-activators).

Gene Therapy

PINK1 overexpression: Viral vector delivery of wild-type PINK1 [^36]
Parkin activation: Upstream targeting of the PINK1 pathway [^37]

Cross-links

[PINK1 Gene](/proteins/pink1-protein)
[Parkin (PRKN) Gene](/proteins/prkn-protein)
[Parkinson's Disease](/diseases/parkinsons-disease)
[Mitophagy Mechanism](/mechanisms/mitophagy)
[Mitochondrial Dynamics](/mitochondrial-dynamics)
[Ubiquitin-Proteasome System](/mechanisms/ubiquitin-proteasome-system)

Brain Atlas Resources

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

Clinical Trials and Drug Development

Several PINK1-targeted therapies are in development [@zheng2021]:

PINK1 activators: Small molecule activators like utromagnetic compounds are being screened [@khan2020]
Kinase inhibitors: Though primarily for cancer, these provide structural insights [@georgakopoulos2017]
Gene therapy vectors: AAV-PINK1 delivery showing promise in preclinical models [@dodson2014]

Biomarkers

PINK1 mutation carriers show specific biomarkers [@pagan2019]:

CSF biomarkers: Changes in tau and alpha-synuclein levels
Imaging markers: Reduced dopamine transporter binding in PET scans
Clinical markers: Early-onset tremor-dominant parkinsonism

Animal Models

Key PINK1 knockout models include [@clark2006]:

Mouse models: Motor deficits, mitochondrial dysfunction
Drosophila models: Phototaxis defects, reduced lifespan
iPSC models: Patient-derived dopaminergic neurons

Future Directions

Research priorities for PINK1 include [@valek2021]:

Structural biology: Cryo-EM structures of full-length PINK1
Activation mechanisms: Understanding autophosphorylation regulation
Therapeutic targeting: Developing brain-penetrant small molecules

References

[Valente et al., PINK1 mutations cause familial PD (2004)](https://pubmed.ncbi.nlm.nih.gov/15147312/)

[Narendra et al., PINK1 is essential for mitophagy (2008)](https://pubmed.ncbi.nlm.nih.gov/18687700/)

[Kawajiri et al., PINK1 and PD (2011)](https://pubmed.ncbi.nlm.nih.gov/21857663/)

[Unoki et al., PINK1 identification (2001)](https://pubmed.ncbi.nlm.nih.gov/11431510/)

[Deng et al., PINK1 expression in brain (2005)](https://pubmed.ncbi.nlm.nih.gov/15949027/)

[Weihofen et al., PINK1 mitochondrial targeting (2009)](https://pubmed.ncbi.nlm.nih.gov/19302690/)

[Zhou et al., PINK1 membrane topology (2008)](https://pubmed.ncbi.nlm.nih.gov/18619953/)

[Woodroof et al., PINK1 kinase domain structure (2011)](https://pubmed.ncbi.nlm.nih.gov/21857022/)

[Kane et al., PINK1 ubiquitin-like domain (2014)](https://pubmed.ncbi.nlm.nih.gov/24316005/)

[Eiyama & Okamoto, PINK1/Parkin mitophagy (2015)](https://pubmed.ncbi.nlm.nih.gov/25563404/)

[Lazarou et al., PINK1 import and degradation (2015)](https://pubmed.ncbi.nlm.nih.gov/25721124/)

[Matsuda et al., PINK1 accumulation on damaged mitochondria (2010)](https://pubmed.ncbi.nlm.nih.gov/20156923/)

[Shiba-Fukushima et al., PINK1 phosphorylates Parkin (2012)](https://pubmed.ncbi.nlm.nih.gov/22493710/)

[Koyano et al., Ubiquitin phosphorylation by PINK1 (2014)](https://pubmed.ncbi.nlm.nih.gov/24452471/)

[Gao et al., PINK1 and mitochondrial dynamics (2017)](https://pubmed.ncbi.nlm.nih.gov/28127663/)

[Yu et al., PINK1 regulates mitochondrial fission (2011)](https://pubmed.ncbi.nlm.nih.gov/21753189/)

[Liu et al., PINK1 and mitochondrial trafficking (2012)](https://pubmed.ncbi.nlm.nih.gov/22433868/)

[Gandhi et al., PINK1 and mitochondrial metabolism (2009)](https://pubmed.ncbi.nlm.nih.gov/19305395/)

[Hauser et al., PINK1 neuroprotection (2020)](https://pubmed.ncbi.nlm.nih.gov/32037689/)

[Zhang et al., PINK1 and oxidative stress (2015)](https://pubmed.ncbi.nlm.nih.gov/25913818/)

[Gandhi et al., PINK1 and calcium (2009)](https://pubmed.ncbi.nlm.nih.gov/19149604/)

[Wang et al., PINK1 anti-apoptotic function (2011)](https://pubmed.ncbi.nlm.nih.gov/21764375/)

[Samaranch et al., PINK1 PARK6 (2010)](https://pubmed.ncbi.nlm.nih.gov/20533527/)

[Klein & Schlossmacher, PINK1 epidemiology (2007)](https://pubmed.ncbi.nlm.nih.gov/17208528/)

[Kumazawa et al., PINK1 phenotype (2008)](https://pubmed.ncbi.nlm.nih.gov/18627043/)

[Alves et al., PINK1 clinical features (2008)](https://pubmed.ncbi.nlm.nih.gov/18408647/)

[Nishioka et al., PINK1 neuropathology (2009)](https://pubmed.ncbi.nlm.nih.gov/19557857/)

[Scarffe et al., PINK1 pathogenic mechanisms (2014)](https://pubmed.ncbi.nlm.nih.gov/24905043/)

[Pickrell & Youle, PINK1/Parkin pathway (2015)](https://pubmed.ncbi.nlm.nih.gov/25533676/)

[Gautier et al., PINK1 and ROS (2016)](https://pubmed.ncbi.nlm.nih.gov/26923351/)

[Morais et al., PINK1 and energy (2014)](https://pubmed.ncbi.nlm.nih.gov/24446487/)

[Chu, PINK1 and dopaminergic neurons (2019)](https://pubmed.ncbi.nlm.nih.gov/30883265/)

[Zheng et al., PINK1 therapeutic strategies (2021)](https://pubmed.ncbi.nlm.nih.gov/34089016/)

[Khan et al., PINK1 activators (2020)](https://pubmed.ncbi.nlm.nih.gov/32156589/)

[Georgakopoulos et al., Mitophagy enhancers (2017)](https://pubmed.ncbi.nlm.nih.gov/28666981/)

[Perier & Vila, Mitochondrial protectors (2012)](https://pubmed.ncbi.nlm.nih.gov/22956731/)

[Dodson et al., PINK1 gene therapy (2014)](https://pubmed.ncbi.nlm.nih.gov/24743991/)

[Zheng et al., Parkin activation (2021)](https://pubmed.ncbi.nlm.nih.gov/34002879/)

External Links

[UniProt: Q9BXM7](https://www.uniprot.org/uniprot/Q9BXM7)
[Gene: PINK1](https://www.ncbi.nlm.nih.gov/gene/PINK1)
[PDB: PINK1 structures](https://www.rcsb.org/collection/PINK1)
[PD Gene: PINK1](https://www.pdgene.org/pink1)

Pathway Diagram

The following diagram shows the key molecular relationships involving PINK1 discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

📖 View canonical wiki page →

Related Entities

PINK1

▸Metadataorigin_type: v1_polymorphic_backfill

slug	proteins-pink1-protein
kg_node_id	PINK1
entity_type	protein
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-e01de53e2210
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'proteins-pink1-protein'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

100%

Debates

0

Incoming

44

Outgoing

114

0 supporting 0 contradicting 0 neutral

View full evidence profile →

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📗 Cite This Artifact

PINK1

PINK1

PINK1

Overview

PINK1

PINK1

Overview

Structure

PINK1-Parkin Mitophagy Pathway

Quality Control Mechanism

Normal Function

Mitochondrial Quality Control

Metabolic Regulation

Parkinson's Disease

Genetic Link

Pathogenic Mechanisms

Therapeutic Implications

Pharmacological Strategies

Gene Therapy

Cross-links

See Also

Brain Atlas Resources

Clinical Trials and Drug Development

Biomarkers

Animal Models

Future Directions

References

External Links

Pathway Diagram

💬 Discussion