Serine/threonine-protein kinase PINK1, mitochondrial

UniProt Q9BXM7 Organism Homo sapiens Gene PINK1 EC 2.7.11.1

Also known as: PINK1

Function

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. 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. 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. 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. 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. This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes. Also promotes mitochondrial fission independently of PRKN and ATG7-mediated mitophagy, via the phosphorylation and activation of DNM1L. 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. 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.

Classification

Family (Pfam): PF00069 Pkinase
InterPro: Kinase-like_dom_sf, MitoQC_Scaffold_Kinases, PINK1_STKc, Prot_kinase_dom, Ser/Thr_kinase_AS
Functional cluster: Zinc-Finger & Ubiquitination Proteins

Experimental structures · PDB · 6

9EIH EM 3.10A
9EII EM 2.75A
9EIJ EM 3.30A
9KMR EM 2.98A
9KOX EM 4.43A
9KQN EM 2.84A

A predicted model is available from AlphaFold.

Gene Ontology · 92

Disease associations

late-onset Parkinson disease MONDO:0008199
autosomal recessive early-onset Parkinson disease 6 MONDO:0011613

Neighborhood · nearest proteins

Nearest neighbours of Serine/threonine-protein kinase PINK1, mitochondrial: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

E3 ubiquitin-protein ligase parkin 18 shared papers
Serine/threonine-protein kinase PINK1, mitochondrial 9 shared papers
Mitochondrial import receptor subunit TOM70 3 shared papers
BRCA1-associated protein 1 shared papers
Parkinson disease protein 7 4 shared papers
Mitochondrial import inner membrane translocase subunit Tim23 1 shared papers
Mitochondrial import receptor subunit TOM20 homolog 4 shared papers
E3 ubiquitin-protein ligase parkin 7 shared papers
Serine/threonine-protein kinase Pink1, mitochondrial 6 shared papers
Ankyrin repeat and BTB/POZ domain-containing protein 1 1 shared papers
Ankyrin repeat and BTB/POZ domain-containing protein 1 1 shared papers
NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mitochondrial 1 shared papers

Literature · 62 cited papers

Structure of human PINK1 at a mitochondrial TOM-VDAC array. Science · 2025
Mechanism of human PINK1 activation at the TOM complex in a reconstituted system. Sci. Adv. · 2024
Tom20 gates PINK1 activity and mediates its tethering of the TOM and TIM23 translocases upon mitochondrial stress. Proc. Natl. Acad. Sci. U.S.A. · 2024
TIM23 facilitates PINK1 activation by safeguarding against OMA1-mediated degradation in damaged mitochondria. Cell Rep. · 2023
The role of the individual TOM subunits in the association of PINK1 with depolarized mitochondria. J. Mol. Med. · 2022
PINK1 phosphorylates Drp1S616 to regulate mitophagy-independent mitochondrial dynamics. EMBO Rep. · 2020
Decision between mitophagy and apoptosis by Parkin via VDAC1 ubiquitination. Proc. Natl. Acad. Sci. U.S.A. · 2020
Rewiring of the Human Mitochondrial Interactome during Neuronal Reprogramming Reveals Regulators of the Respirasome and Neurogenesis. IScience · 2019
Reciprocal roles of Tom7 and OMA1 during mitochondrial import and activation of PINK1. Mol. Cell · 2019
PINK1-mediated phosphorylation of LETM1 regulates mitochondrial calcium transport and protects neurons against mitochondrial stress. Nat. Commun. · 2017
Ubiquitin Ser65 phosphorylation affects ubiquitin structure, chain assembly and hydrolysis. EMBO J. · 2015
Phosphorylation of mitochondrial polyubiquitin by PINK1 promotes Parkin mitochondrial tethering. PLoS Genet. · 2014
… and 50 more in the literature graph

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