Anti-PINK1 antibody [N4/15]

Target data

Serine/threonine-protein kinase which acts as a sensor of mitochondrial damage and protects against mitochondrial dysfunction during cellular stress. 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). 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 ubiquinates 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). 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).