ArticleBMC cell biology2010
Structural determinants of PINK1 topology and dual subcellular distribution.
Article in BMC cell biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Molecular mechanism of PINK1 regulation by the Hsp90 machinery.Nature communications · 2025Article
- PINK1 Immunoexpression Predicts Survival in Patients Undergoing Hepatic Resection for Colorectal Liver Metastases.International journal of molecular sciences · 2023Article
- Article
- The inhibition of PGAM5 suppresses seizures in a kainate-induced epilepsy modelFrontiers in molecular neuroscience · 2022Article
- Mechanisms of microRNA‑142 in mitochondrial autophagy and hippocampal damage in a rat model of epilepsy.International journal of molecular medicine · 2021Article
- Deciphering the dual role and prognostic potential of PINK1 across cancer types.Neural regeneration research · 2021Article
- Role of Cleaved PINK1 in Neuronal Development, Synaptogenesis, and Plasticity: Implications for Parkinson's Disease.Frontiers in neuroscience · 2021Review
- Dependence of PINK1 accumulation on mitochondrial redox system.Aging cell · 2020Article
- Trumping neurodegeneration: Targeting common pathways regulated by autosomal recessive Parkinson's disease genes.Experimental neurology · 2017Review
- The PINK1 p.I368N mutation affects protein stability and ubiquitin kinase activity.Molecular neurodegeneration · 2017Article
- PINK1 Primes Parkin-Mediated Ubiquitination of PARIS in Dopaminergic Neuronal Survival.Cell reports · 2017Article
- Differential submitochondrial localization of PINK1 as a molecular switch for mediating distinct mitochondrial signaling pathways.Cellular signalling · 2015Article
- Unconventional PINK1 localization to the outer membrane of depolarized mitochondria drives Parkin recruitment.Journal of cell science · 2015Article
- Intramembrane protease PARL defines a negative regulator of PINK1- and PARK2/Parkin-dependent mitophagy.Autophagy · 2015Article
- Beyond the mitochondrion: cytosolic PINK1 remodels dendrites through protein kinase A.Journal of neurochemistry · 2014Article
- Article
- Structure and Function of Parkin, PINK1, and DJ-1, the Three Musketeers of Neuroprotection.Frontiers in neurology · 2013Article
- Inactivation of Pink1 gene in vivo sensitizes dopamine-producing neurons to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and can be rescued by autosomal recessive Parkinson disease genes, Parkin or DJ-1.The Journal of biological chemistry · 2012Article
- Pink1 kinase and its membrane potential (Deltaψ)-dependent cleavage product both localize to outer mitochondrial membrane by unique targeting mode.The Journal of biological chemistry · 2012Article
- Microtubule affinity-regulating kinase 2 (MARK2) turns on phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) at Thr-313, a mutation site in Parkinson disease: effects on mitochondrial transport.The Journal of biological chemistry · 2012Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPINK1 is a mitochondria-targeted kinase that constitutively localizes to both the mitochondria and the cytosol. The mechanism of how PINK1 achieves cytosolic localization following mitochondrial processing remains unknown. Understanding PINK1 subcellular localization will give us insights into PINK1 functions and how mutations in PINK1 lead to Parkinson's disease. We asked how the mitochondrial localization signal, the transmembrane domain, and the kinase domain participate in PINK1 localization.
resultsWe confirmed that PINK1 mitochondrial targeting signal is responsible for mitochondrial localization. Once inside the mitochondria, we found that both PINK1 transmembrane and kinase domain are important for membrane tethering and cytosolic-facing topology. We also showed that PINK1 dual subcellular distribution requires both Hsp90 interaction with the kinase domain and the proteolysis at a cleavage site downstream of the transmembrane domain because removal of this cleavage site completely abolished cytosolic PINK1. In addition, the disruption of the Hsp90-PINK1 interaction increased mitochondrial PINK1 level.
conclusionTogether, we believe that once PINK1 enters the mitochondria, PINK1 adopts a tethered topology because the transmembrane domain and the kinase domain prevent PINK1 forward movement into the mitochondria. Subsequent proteolysis downstream of the transmembrane domain then releases PINK1 for retrograde movement while PINK1 kinase domain interacts with Hsp90 chaperone. The significance of this dual localization could mean that PINK1 has compartmental-specific functions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.