ArticleCell research2018
PTEN-L is a novel protein phosphatase for ubiquitin dephosphorylation to inhibit PINK1-Parkin-mediated mitophagy.
Article in Cell research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 109 papers, 2 of them syntheses that pooled it.
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Who cites it
109 citing papers in PubMed, 2 syntheses or guidelines pooled it, 177 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Selective autophagy of intracellular organelles: recent research advances.Theranostics · 2021Pooled it
- USP18 exacerbates myocardial I/R injury by inhibiting Parkin mitophagy through the deubiquitinase PTEN-L.Military Medical Research · 2026Article
- PTEN-L inhibits mitophagy and GSDME-dependent pyroptosis via Parkin dephosphorylation.EMBO reports · 2026Article
- Phosphatase and tensin homolog: A potential target for therapeutic intervention in optic nerve regeneration.Neural regeneration research · 2026Article
- The role of phospho-ubiquitin in mitochondrial health and diseases.The Journal of biological chemistry · 2026Review
- NCBP2 Regulates PGAM5-Mediated Mitophagy Via KIF23 Alternative Splicing To Promote Cervical Cancer ProgressionRun Title: NCBP2 Promotes Cervical Cancer Via Mitophagy.Applied biochemistry and biotechnology · 2026Article
- The Interaction Between Mitophagy Dysregulation and the Diabetic Bladder Microenvironment.Journal of diabetes · 2026Review
- Modulation of mitochondrial quality control in sepsis by traditional Chinese medicine: mechanistic insights and translational perspectives.Frontiers in pharmacology · 2026Review
- Mitophagy in the pathogenesis and management of disease.Cell research · 2026Review
- Mapping the global research landscape of mitophagy in Parkinson's disease: a bibliometric and visualization analysis.Hereditas · 2025Article
- Rho kinase isoforms in neurodegeneration: from cellular functions to therapeutic targets.Molecular biology reports · 2025Review
- Article
- Autophagy and Cellular Senescence in Alzheimer's Disease: Key Drivers of Neurodegeneration.CNS neuroscience & therapeutics · 2025Review
- Furin inhibits HSCs activation and ameliorates liver fibrosis by regulating PTEN-L/PINK1/parkin mediated mitophagy in mouse.FASEB bioAdvances · 2025Article
- Targeting mitophagy in neurodegenerative diseases.Nature reviews. Drug discovery · 2025Review
- A positive feedback loop between SMAD3 and PINK1 in regulation of mitophagy.Cell discovery · 2025Article
- Glucose-6-phosphate dehydrogenase regulates mitophagy by maintaining PINK1 stability.Life metabolism · 2025Article
- Mitochondrial microRNAs: Key Drivers in Unraveling Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Overexpression of Parkin promotes the protective effect of mitochondrial autophagy on the lung of rats with exertional heatstroke.Journal of intensive medicine · 2025Article
49 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
28 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitophagy is an important type of selective autophagy for specific elimination of damaged mitochondria. PTEN-induced putative kinase protein 1 (PINK1)-catalyzed phosphorylation of ubiquitin (Ub) plays a critical role in the onset of PINK1-Parkin-mediated mitophagy. Phosphatase and tensin homolog (PTEN)-long (PTEN-L) is a newly identified isoform of PTEN, with addition of 173 amino acids to its N-terminus. Here we report that PTEN-L is a novel negative regulator of mitophagy via its protein phosphatase activity against phosphorylated ubiquitin. We found that PTEN-L localizes at the outer mitochondrial membrane (OMM) and overexpression of PTEN-L inhibits, whereas deletion of PTEN-L promotes, mitophagy induced by various mitochondria-damaging agents. Mechanistically, PTEN-L is capable of effectively preventing Parkin mitochondrial translocation, reducing Parkin phosphorylation, maintaining its closed inactive conformation, and inhibiting its E3 ligase activity. More importantly, PTEN-L reduces the level of phosphorylated ubiquitin (pSer65-Ub) in vivo, and in vitro phosphatase assay confirms that PTEN-L dephosphorylates pSer65-Ub via its protein phosphatase activity, independently of its lipid phosphatase function. Taken together, our findings demonstrate a novel function of PTEN-L as a protein phosphatase for ubiquitin, which counteracts PINK1-mediated ubiquitin phosphorylation leading to blockage of the feedforward mechanisms in mitophagy induction and eventual suppression of mitophagy. Thus, understanding this novel function of PTEN-L provides a key missing piece in the molecular puzzle controlling mitophagy, a critical process in many important human diseases including neurodegenerative disorders such as Parkinson's disease.
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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.