PINK1 Products

Description

Phosphatase and Tensin Homolog (PTEN) is a tumor suppressor which acts as an antagonist to phosphatidylinositol 3-kinase (PI3K) signaling. PTEN exerts enzymatic activity as a phosphatidylinositol-3,4,5-trisphosphate (PIP3) phosphatase, opposing PI3K activity by reducing availability of PIP3 to proliferating cells. Loss of PTEN function leads to elevated PIP3 and increased activation of PI3K/AKT signaling in many types of cancer.

PINK1 (PTEN induced putative kinase 1) protein contains a N-terminal mitochondrial targeting sequence, putative transmembrane helix, linker region, serine (Ser65)/threonine (Thr257) kinase domain and C-terminal segment. PINK1 is translated in the cytosol, then translocated to the outer mitochondrial membrane where it is rapidly cleaved and degraded as a part of normal mitochondrial function. In damaged (depolarized) mitochondria, PINK1 becomes stabilized and accumulates, resulting in the subsequent phosphorylation of numerous proteins on the mitochondrial surface.

When PINK1 is imported into the cell, mitochondrial processing peptidase, presenilin-associated rhomboid-like protease and AFG3L2 cleave PINK1 and tag it for the ubiquitin-proteasome pathway, keeping low PINK1 protein expression at basal conditions (1,2). Accumulation of PINK1 in mitochondria indicate damage. PINK1 maintains mitochondrial function/integrity, provides protection against mitochondrial dysfunction during cellular stress, and is involved in the clearance of damaged mitochondria via selective autophagy (mitophagy) (3). PINK1 has a theoretical molecular weight of 63 kDa and undergoes proteolytic processing to generate at least two cleaved forms (55 kDa and 42 kDa).

Ultimately PARK2 (E3 Ubiquitin Ligase Parkin) is recruited to the damaged mitochondria where it is activated by 1) PINK-mediated phosphorylation of PARK2 at serine 65, and 2) PARK2 interaction with phosphorylated ubiquitin (also phosphorylated by PINK1 on serine 65) (4,5). There is a strong interplay between Parkin and PINK1, where loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by Parkin (2,4,5). Mutations in either Parkin or PINK1 alter mitochondrial turnover, resulting in the accumulation of defective mitochondria and, ultimately, neurodegeneration in Parkinson's disease. Mutations in the PINK1 gene located within the PARK6 locus on chromosome 1p35-p36 have been identified in patients with early-onset Parkinson's disease (6).

References

1.Rasool, S., Soya, N., Truong, L., Croteau, N., Lukacs, G. L., & Trempe, J. F. (2018). PINK1 autophosphorylation is required for ubiquitin recognition. EMBO Rep, 19(4). doi:10.15252/embr.201744981

2.Shiba-Fukushima, K., Arano, T., Matsumoto, G., Inoshita, T., Yoshida, S., Ishihama, Y., . . . Imai, Y. (2014). Phosphorylation of mitochondrial polyubiquitin by PINK1 promotes Parkin mitochondrial tethering. PLoS Genet, 10(12), e1004861. doi:10.1371/journal.pgen.1004861

3.Vives-Bauza, C., Zhou, C., Huang, Y., Cui, M., de Vries, R. L., Kim, J., . . . Przedborski, S. (2010). PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci U S A, 107(1), 378-383. doi:10.1073/pnas.0911187107

4.McWilliams, T. G., Barini, E., Pohjolan-Pirhonen, R., Brooks, S. P., Singh, F., Burel, S., . . . Muqit, M. M. K. (2018). Phosphorylation of Parkin at serine 65 is essential for its activation in vivo. Open Biol, 8(11). doi:10.1098/rsob.180108

5.Exner, N., Treske, B., Paquet, D., Holmstrom, K., Schiesling, C., Gispert, S., . . . Haass, C. (2007). Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin. J Neurosci, 27(45), 12413-12418. doi:10.1523/jneurosci.0719-07.2007

6.Valente, E. M., Bentivoglio, A. R., Dixon, P. H., Ferraris, A., Ialongo, T., Frontali, M., . . . Wood, N. W. (2001). Localization of a novel locus for autosomal recessive early-onset parkinsonism, PARK6, on human chromosome 1p35-p36. Am J Hum Genet, 68(4), 895-900. doi:10.1086/319522

Bioinformatics

Entrez	298575 Rat 65018 Human 68943 Mouse
Uniprot	AAH28215 Human AAH28215.1 Human NP_115785 Human NP_115785.1 Human Q99MQ3 Mouse Q9BXM7 Human
Product By Gene ID	65018
Alternate Names	BRPK EC 2.7.11.1 FLJ27236 PARK6 Parkinson disease (autosomal recessive) 6 protein kinase BRPK PTEN Induced Kinase 1 PTEN induced putative kinase 1 PTEN-induced putative kinase protein 1 serine/threonine-protein kinase PINK1, mitochondrial

Research Areas for PINK1

Find related products by research area and learn more about each of the different research areas below.

Alzheimers Research
DNA Repair
Lipid and Metabolism
Mitochondrial Markers
Neurodegeneration
Neuronal Cell Markers
Neuroscience
Protein Kinase
Signal Transduction

Related PINK1 Blog Posts

Check out the latest blog posts on PINK1.

The identification of dopaminergic neurons using Tyrosine Hydroxylase in Parkinson's research and LRRK2 Tyrosine hydroxylase (TH) is a crucial enzyme involved in the biosynthesis of dopamine, norepinephrine and epinephrine in the brain.  Specifically, TH catalyzes the conversion of l-tyrosine to l-dihydroxyphenylalanine (l-dopa).  The importance of t...    Read more.

The role of Parkin and autophagy in retinal pigment epithelial cell (RPE) degradation The root of Parkinson’s disease (PD) points to a poorly regulated electron transport chain leading to mitochondrial damage, where many proteins need to work cohesively to ensure proper function.  The two key players of this pathway are PINK1, ...    Read more.

PINK1: All work and no fun The protein PINK1 is a mitochondrial-located serine/threonine kinase (PTK) that maintains organelle function and integrity. It not only protects organelles from cellular stress, but it also uses the selective auto-phagocytosis process for cleaning and...    Read more.

PINK1: A Critical Player in Mitophagy PINK1 (PTEN-induced putative kinase 1) is a mitochondrial directed serine-threonine kinase, that regulates normal mitochondrial function and transport vital to normal performance of neurons and neuronal survival. PINK1 has been shown to be localized t...    Read more.

PINK1: Linking Mitochondrial Health and Parkinson's disease Parkinson's disease is a degenerative disorder of the central nervous system, which involves the loss of dopaminergic neurons in the brain and gives rise to tremors, rigidity and slowness of movement. In the majority of cases there is no known cause; ...    Read more.

PINK1: Promoting Organelle Stability and Preventing Parkinson's disease PINK1 is a protein serine/threonine kinase (PTK) that protects the organelles from cellular stress and controls selective autophagy to clear damage. Exner, et. al. were among the first to report that PINK1 deficiency in humans was linked to autosomal ...    Read more.

PINK1: Promoting Organelle Stability and Preventing Parkinson's disease PINK1 is a protein serine/threonine kinase (PTK) that protects the organelles from cellular stress and controls selective autophagy to clear damage. Exner, et al. were among the first to report that PINK1 deficiency in humans was linked to autosomal r...    Read more.

There's an autophagy for that! By Christina Towers, PhDA critical mechanism that cells use to generate nutrients and fuel metabolism is through a process called autophagy.  This process is complex and involves over 20 different proteins, most of which are highly conserved acro...    Read more.

Losing memory: Toxicity from mutant APP and amyloid beta explain the hippocampal neuronal damage in Alzheimer's disease  By Jamshed Arslan Pharm.D.  Alzheimer's disease (AD) is an irreversible brain disorder that destroys memory and thinking skills. The telltale signs of AD brains are extracellular deposits of amy...    Read more.

PINK1 and its role in Parkinson's disease PINK1 (PTEN induced putative kinase 1) is a mitochondrial serine/threonine kinase which maintains mitochondrial function/integrity, provides protection against mitochondrial dysfunction during cellular stress, potentially by phosphorylating mitochondr...    Read more.

New Players in the Mitophagy Game By Christina Towers, PhD Mitochondrial turn over via the lysosome, otherwise known as mitophagy, involves engulfment of mitochondria into double membrane autophagosomes and subsequent fusion with lysosomes. Much is al...    Read more.

Understanding Mitophagy Mechanisms: Canonical PINK1/Parkin, LC3-Dependent Piecemeal, and LC3-Independent Mitochondrial Derived Vesicles By Christina Towers, PhD What is Mitophagy?The selective degradation of mitochondria via double membrane autophagosome vesicles is called mitophagy. Damaged mitochondria can generate harmful amounts of reactive ox...    Read more.

PINK1 - performing mitochondrial quality control and protecting against Parkinson’s disease PTEN-induced putative kinase 1 (PINK1) is a serine/threonine kinase with important functions in mitochondrial quality control. Together with the Parkin protein, PINK1 is able to regulate the selective degradation of damaged mitochondria through aut...    Read more.

Parkin - Role in Mitochondrial Quality Control and Parkinson's Disease Parkin/PARK2 is a cytosolic enzyme which gets recruited to cellular mitochondria damaged through depolarization, ROS or unfolded proteins accumulation, and exert protective effects by inducing mitophagy (mitochondrial autophagy). Parkin induces mit...    Read more.

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