Summary

Name PINK1
Full Name Serine/threonine-protein kinase PINK1, mitochondrial
Synonyms BRPK, PTEN-induced putative kinase protein 1
Primary ID Q9BXM7
Links - -
Type protein
Relations 29
Pathways Parkinson
Function Serine/threonine-protein kinase which protects against mitochondrial dysfunction during cellular stress by phosphorylating mitochondrial proteins such as PRKN and DNM1L, to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components (PubMed:14607334, PubMed:18957282, PubMed:18443288, PubMed:15087508, PubMed:19229105, PubMed:19966284, PubMed:20404107, PubMed:22396657, PubMed:20798600, PubMed:23620051, PubMed:23754282, PubMed:23933751, PubMed:24660806, PubMed:24898855, PubMed:24751536, PubMed:24784582, PubMed:24896179, PubMed:25527291, PubMed:32484300, PubMed:20547144). Depending on the severity of mitochondrial damage and/or dysfunction, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to regulating mitochondrial dynamics and eliminating severely damaged mitochondria via mitophagy (PubMed:18443288, PubMed:23620051, PubMed:24898855, PubMed:20798600, PubMed:20404107, PubMed:19966284, PubMed:32484300, PubMed:22396657, PubMed:32047033, PubMed:15087508). Mediates the translocation and activation of PRKN at the outer membrane (OMM) of dysfunctional/depolarized mitochondria (PubMed:19966284, PubMed:20404107, PubMed:20798600, PubMed:23754282, PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25474007, PubMed:25527291). At the OMM of damaged mitochondria, phosphorylates pre-existing polyubiquitin chains at 'Ser-65', the PINK1-phosphorylated polyubiquitin then recruits PRKN from the cytosol to the OMM where PRKN is fully activated by phosphorylation at 'Ser-65' by PINK1 (PubMed:19966284, PubMed:20404107, PubMed:20798600, PubMed:23754282, PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25474007, PubMed:25527291). In damaged mitochondria, mediates the decision between mitophagy or preventing apoptosis by promoting PRKN-dependent poly- or monoubiquitination of VDAC1; polyubiquitination of VDAC1 by PRKN promotes mitophagy, while monoubiquitination of VDAC1 by PRKN decreases mitochondrial calcium influx which ultimately inhibits apoptosis (PubMed:32047033). When cellular stress results in irreversible mitochondrial damage, functions with PRKN to promote clearance of damaged mitochondria via selective autophagy (mitophagy) (PubMed:14607334, PubMed:20798600, PubMed:20404107, PubMed:19966284, PubMed:23933751, PubMed:15087508). The PINK1-PRKN pathway also promotes fission of damaged mitochondria by phosphorylating and thus promoting the 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).

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▶Modifications Tables

Relations

Regulator Mechanism target score ℹ
+ PINK1down-regulates activity img/direct_inhibition.png phosphorylation RAB8A 0.273
Publications: 1 Organism: In Vitro
+ PINK1up-regulates img/direct-activation.png phosphorylation HTRA2 0.612
Publications: 1 Organism: Homo Sapiens
Pathways:Parkinson
+ PINK1down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation RHOT1 0.776
Publications: 2 Organism: Homo Sapiens
+ PINK1down-regulates activity img/direct_inhibition.png phosphorylation PTEN 0.474
Publications: 1 Organism: Homo Sapiens
+ PINK1down-regulates activity img/direct_inhibition.png phosphorylation TUFM 0.2
Publications: 1 Organism: Homo Sapiens
+ PINK1down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation ZNF746 0.373
Publications: 2 Organism: Homo Sapiens
+ PINK1up-regulates activity img/direct-activation.png phosphorylation ZNF746 0.373
Publications: 2 Organism: Homo Sapiens
+ PINK1up-regulates activity img/direct-activation.png phosphorylation TP53 0.324
Publications: 1 Organism: Homo Sapiens
+ PINK1down-regulates quantity img/direct_inhibition.png phosphorylation MFN2 0.81
Publications: 1 Organism: Homo Sapiens
+ PINK1up-regulates activity img/direct-activation.png phosphorylation PRKN 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:Parkinson
+ PINK1up-regulates img/direct-activation.png phosphorylation UBA52 0.38
Publications: 1 Organism: Mus Musculus
+ PINK1up-regulates img/direct-activation.png phosphorylation PRKN 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:Parkinson
+ PINK1up-regulates img/direct-activation.png phosphorylation Ubiquitin 0.601
Publications: 1
+ PINK1up-regulates activity img/direct-activation.png phosphorylation UBC 0.601
Publications: 1 Organism: Homo Sapiens
Pathways:Parkinson
+ PINK1down-regulates activity img/direct_inhibition.png phosphorylation HIF3A 0.35
Publications: 1 Organism: Homo Sapiens
+ PINK1up-regulates activity img/direct-activation.png phosphorylation LETM1 0.361
Publications: 1 Organism: In Vitro
+ MARK2up-regulates activity img/direct-activation.png phosphorylation PINK1 0.368
Publications: 1 Organism: In Vitro
+ PARLdown-regulates quantity by destabilization img/direct_inhibition.png cleavage PINK1 0.618
Publications: 1 Organism: Homo Sapiens
+ PMPCBdown-regulates quantity by destabilization img/direct_inhibition.png cleavage PINK1 0.341
Publications: 1 Organism: Homo Sapiens
+ PINK1down-regulates quantity img/indirect_inhibition.png ubiquitination MFN1 0.698
Publications: 1 Organism: Homo Sapiens
+ PINK1up-regulates activity img/direct-activation.png phosphorylation TRAP1 0.617
Publications: 1 Organism: Homo Sapiens
+ PTENup-regulates quantity by expression img/indirect-activation.png transcriptional regulation PINK1 0.474
Publications: 1 Organism: Homo Sapiens
+ PINK1down-regulates quantity img/indirect_inhibition.png ubiquitination MFN2 0.81
Publications: 1 Organism: Homo Sapiens
+ PINK1down-regulates quantity img/direct_inhibition.png CYCS 0.386
Publications: 1 Organism: Homo Sapiens
Pathways:Parkinson
+ IMMTup-regulates activity img/direct-activation.png binding PINK1 0.402
Publications: 1 Organism: In Vitro
+ PINK1down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation RHOT2 0.719
Publications: 1 Organism: Homo Sapiens