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 mitochondrial proteins, and is involved in the clearance of damaged mitochondria via selective autophagy (mitophagy). PINK1 and its substrates have been found in the cytosol as well as in different sub-mitochondrial compartments. According to recent reports, PINK1 may be targeted to OMM (outer mitochondrial membrane) with its kinase domain facing the cytosol, providing a possible explanation for the observed physical interaction with the cytosolic E3 ubiquitin ligase Parkin. PINK1 has been linked to autosomal recessive early onset Parkinson's disease, Alzheimer's disease, dementia, multiple sclerosis, schizophrenia, neuronitis, myeloma ect.
Parkinson's disease (PD) is a progressive and irreversible neurodegenerative disorder coupled to selective degeneration of dopamine-producing neurons in the substantia nigra. Mutations in PINK1 cause autosomal recessive forms of early-onset PD and PINK1 stimulates Omi/HtrA2/PARK13 protease activity when both proteins act as neuroprotective components in the same stress pathway. Although PARK13-mediated protective mechanisms are at least in part regulated by PINK1, little is known concerning how these two proteins are regulated in different subcellular compartments. Recent study has indicated a correlative relationship between the two proteins. Moreover, they showed that PARK13 and PINK1 protein levels accumulate in response to H2 O2 and L-DOPA treatments in a subcellular fashion and that both proteins show relocation to the cytoskeleton in response to H2 O2 . This study shows that PARK13 and PINK1 are subcellular-specific but dynamic proteins with a reciprocal molecular relationship providing new insight into the complexity of PD. (1)
Immunocytochemistry/Immunofluorescence: PINK1 Antibody
The mitochondrial kinase PINK1 and the ubiquitin ligase Parkin participate in quality control after CCCP- or ROS-induced mitochondrial damage, and their dysfunction is associated with the development and progression of Parkinson's disease. Furthermore, PINK1 expression is also induced by starvation indicating an additional role for PINK1 in stress response. Therefore, the effects of PINK1 deficiency on the autophagy-lysosomal pathway during stress were investigated. PINK1-mediated reduction of autophagic key factors during stress resulted in increased cell death, thus defining an additional pathway that could contribute to the progression of Parkinson's disease in patients with PINK1 mutations. (2)
Another study has shown that mitochondrial impairment increases FL-PINK1 levels by calcium-dependent gene expression suggesting a role for PINK1 in mitophagy that is downstream of ubiquitination of mitochondrial substrates. The sensitivity to intracellular calcium levels supports the hypothesis that PINK1 may also play a role in cellular calcium homeostasis and neuroprotection. (3)
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