PINK1
GeneName
PINK1
Summary
PINK1, also known as PTEN induced putative kinase 1 or PINK-1, is a 63kDa serine/threonine kinase predominantly localised to the mitochondria, including the mitochondrial inner and outer membranes, as well as the cytoplasm and nucleus. It plays a critical role in mitochondrial quality control through processes such as mitophagy, where it helps to eliminate damaged mitochondria. PINK1 is involved in various cellular responses, including those to oxidative stress and hypoxia, and is essential for the maintenance of mitochondrial integrity and function. The protein interacts with multiple partners, including ubiquitin ligases, to regulate mitochondrial dynamics and apoptosis.
Importance
PINK1 is relevant to: - Neurodegenerative diseases, particularly Parkinson's disease, due to its role in mitochondrial function and protection against oxidative stress. - The regulation of autophagy and mitochondrial homeostasis, which are crucial for cellular health. - Understanding the mechanisms of neuronal cell death and survival, providing insights into therapeutic strategies for neuroprotection. - The study of mitochondrial diseases and the development of potential biomarkers for early diagnosis and treatment.
Top Products
For researchers investigating PINK1, we recommend two excellent primary antibodies that cater to a variety of applications. The first is the well-cited Anti-PINK1 antibody [N4/15] (ab186303), a monoclonal antibody that has garnered 35 citations for its reliable performance in Western blotting (WB) and immunocytochemistry (ICC). In addition, we offer the top-selling recombinant antibody, Anti-PINK1 antibody [EPR20730] (ab216144), which has been validated in knockout models and is suitable for WB, ICC, and immunoprecipitation (IP). This antibody stands out with 43 citations, reflecting its growing acceptance in the research community. The recombinant nature of this product ensures batch-to-batch consistency, making it an ideal choice for researchers seeking dependable results in their studies of PINK1.
Abcam Product Citation Summary
The data indicates that PINK1 antibodies were primarily used in Western blotting across various studies involving rat and mouse models. The studies focused on different biological contexts, including the effects of IL-1β treatment and Alzheimer's disease, highlighting the relevance of PINK1 in neurodegenerative conditions and liver function.
Abcam Product Citation Table
Function
Serine/threonine-protein kinase which acts as a sensor of mitochondrial damage and protects against mitochondrial dysfunction during cellular stress (PubMed:40080546). It phosphorylates mitochondrial proteins to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components (PubMed:14607334, PubMed:15087508, PubMed:18443288, PubMed:18957282, PubMed:19229105, PubMed:19966284, PubMed:20404107, PubMed:20547144, PubMed:20798600, PubMed:22396657, PubMed:23620051, PubMed:23754282, PubMed:23933751, PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:24896179, PubMed:24898855, PubMed:25527291, PubMed:32484300). In healthy mitochondria, PINK1 is translocated across the mitochondrial outer membrane (MOM) via the translocase of the outer membrane (TOM) complex, and inserted into the mitochondrial inner membrane (MIM) via the translocase of the inner membrane (TIM23) complex where it is cleaved and released into the cytosol (PubMed:40080546). Depending on the severity of mitochondrial damage, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to eliminating severely damaged mitochondria via PINK1-PRKN-dependent mitophagy (PubMed:14607334, PubMed:15087508, PubMed:18443288, PubMed:19966284, PubMed:20404107, PubMed:20798600, PubMed:22396657, PubMed:23620051, PubMed:23933751, PubMed:24898855, PubMed:32047033, PubMed:32484300). When cellular stress results in irreversible mitochondrial damage, PINK1 accumulates at the outer mitochondrial membrane (OMM) where it phosphorylates pre-existing polyubiquitin chains at 'Ser-65', recruits PRKN from the cytosol to the OMM and activates PRKN by phosphorylation at 'Ser-65'; activated PRKN then ubiquitinates VDAC1 and other OMM proteins to initiate mitophagy (PubMed:14607334, PubMed:15087508, PubMed:19966284, PubMed:20404107, PubMed:20798600, PubMed:23754282, PubMed:23933751, PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25474007, PubMed:25527291, PubMed:32047033, PubMed:40080546). The PINK1-PRKN pathway also promotes fission of damaged mitochondria through phosphorylation and PRKN-dependent degradation of mitochondrial proteins involved in fission such as MFN2 (PubMed:18443288, PubMed:23620051, PubMed:24898855). This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes (PubMed:18443288, PubMed:23620051). Also promotes mitochondrial fission independently of PRKN and ATG7-mediated mitophagy, via the phosphorylation and activation of DNM1L (PubMed:18443288, PubMed:32484300). Regulates motility of damaged mitochondria by promoting the ubiquitination and subsequent degradation of MIRO1 and MIRO2; in motor neurons, this likely inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria undergoing mitophagy in the soma (PubMed:22396657). Required for ubiquinone reduction by mitochondrial complex I by mediating phosphorylation of complex I subunit NDUFA10 (By similarity). Phosphorylates LETM1, positively regulating its mitochondrial calcium transport activity (PubMed:29123128).
Involvement in disease
Parkinson disease 6
PARK6
An early-onset form of Parkinson disease, a neurodegenerative disorder characterized by parkinsonian signs such as rigidity, resting tremor and bradykinesia. A subset of patients manifest additional symptoms including hyperreflexia, autonomic instability, dementia and psychiatric disturbances. Symptoms show diurnal fluctuation and can improve after sleep. PARK6 pathogenesis involves respiratory complex I deficiency causing mitochondrial depolarization and dysfunction. Inheritance is autosomal recessive.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Proteolytically cleaved (PubMed:19229105, PubMed:22354088, PubMed:30733118). In healthy cells, the precursor is continuously imported into the inner mitochondrial membrane (IMM), where it is proteolytically cleaved by mitochondrial-processing peptidase (MPP) and then undergoes further proteolytic cleavage by PARL or AFG3L2 to give rise to the 52 kDa short form (PubMed:19229105, PubMed:22354088). The 52 kDa short form is then released into the cytosol where it rapidly undergoes proteasome-dependent degradation (PubMed:20404107). In unhealthy cells, when cellular stress conditions lead to the loss of mitochondrial membrane potential, mitochondrial import is impaired leading to the precursor accumulating on the outer mitochondrial membrane (OMM) (PubMed:20404107, PubMed:30733118). If accumulation at the OMM fails and it is imported into the depolarized mitochondria, it undergoes cleavage by the IMM protease OMA1, promoting its subsequent degradation by the proteasome (PubMed:30733118).
Autophosphorylated (PubMed:18957282, PubMed:20404107, PubMed:22910362). Loss of mitochondrial membrane potential results in the precursor accumulating on the outer mitochondrial membrane (OMM) where it is activated by autophosphorylation (PubMed:18957282, PubMed:20404107, PubMed:22910362). Autophosphorylation at Ser-228 and Ser-402 is sufficient and essential for selective recruitment of PRKN to depolarized mitochondria, via PINK1-dependent phosphorylation of ubiquitin and maybe PRKN (PubMed:18957282, PubMed:22910362).
Sequence Similarities
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.
Tissue Specificity
Highly expressed in heart, skeletal muscle and testis, and at lower levels in brain, placenta, liver, kidney, pancreas, prostate, ovary and small intestine. Present in the embryonic testis from an early stage of development.
Cellular localization
- Mitochondrion outer membrane
- Mitochondrion inner membrane
- Cytoplasm
- Cytosol
- Localizes mostly in mitochondrion and the two smaller proteolytic processed fragments localize mainly in cytosol (PubMed:19229105). In healthy mitochondria, PINK1 is translocated across the mitochondrial membranes (PubMed:40080546). Upon mitochondrial membrane depolarization following damage, PINK1 import is stalled, which induces its accumulation in the outer mitochondrial membrane and the activation of its kinase activity (PubMed:18957282, PubMed:40080546).
Alternative names
BRPK, PTEN-induced putative kinase protein 1, PINK1