| PINK1 — PTEN Induced Kinase 1 | |
|---|---|
| Symbol | PINK1 |
| Full Name | PTEN Induced Kinase 1 |
| Chromosome | 1p36.12 |
| NCBI Gene | 65018 |
| Ensembl | ENSG00000158828 |
| OMIM | 608309 |
| UniProt | Q9BXM7 |
| Diseases | Parkinson's Disease |
| Expression | Substantia nigra, Cerebral cortex, Mitochondria (widespread) |
| Key Mutations | |
| Q456X, G309D, W437X, E240K, A168P, L347P, M341I, C-terminal mutations | |
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.
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[1]. Pathogenic mutations in PINK1 cause autosomal recessive early-onset Parkinson's Disease, making it one of the most important genes linked to familial PD[2]. 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--TEMP--/proteins)--FIX--, a 581-amino acid kinase that localizes to mitochondria. See the protein page for detailed structural and functional information.
The PINK1 gene spans approximately 1.5 Mb of genomic DNA on chromosome 1p36.12 and consists of 8 exons[3]. The gene produces a single transcript encoding the PINK1 protein kinase.
The PINK1 promoter contains several regulatory elements:
Expression is regulated by:
In the healthy brain, PINK1 is expressed at high levels in:
PINK1 is ubiquitously expressed in all tissues with highest levels in muscle and heart. Expression data is available from the Allen Human Brain Atlas.
PINK1 plays several essential roles in mitochondrial biology:
PINK1 mutations cause autosomal recessive PD through loss of function[4]:
Most pathogenic mutations result in:
The sequence of events in PINK1-linked PD:
| 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 |
PINK1 and PRKN (Parkin) work together in mitochondrial quality control[5]:
Several models have been developed:
Current research focuses on:
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.
[1] Valente EM, Abou-Sleiman PM, Caputo V, et al. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science. 2004;304(5674):1158-1160. DOI:10.1126/science.1096284
[2] Narendra D, Tanaka A, Suen DF, Youle RJ. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol. 2010;8(1):e1000298. DOI:10.1371/journal.pbio.1000298
[3] Greene AW, Grenier K, Aguila MA, et al. Mitochondrial processing peptidase regulates PINK1 processing, import and Parkin recruitment. EMBO Rep. 2012;13(2):133-143.
[4] Park J, Lee SB, Son J, et al. Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature. 2006;441(7097):1157-1161.
[5] Kazlauskaite A, Kondapalli C, Gourlay R, et al. Phosphorylation of Parkin at Serine65 is essential for activation. Biochem J. 2014;462(3):e1-e3.
[6] Lin W, Kang UJ. Characterization of PINK1 (PTEN-induced putative kinase 1) stability, localization, and distribution in the brains of aging mice. Exp Neurol. 2010;225(1):118-126.