ReviewGenes & development2015
The three 'P's of mitophagy: PARKIN, PINK1, and post-translational modifications.
Review in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 226 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
226 citing papers in PubMed, 3 syntheses or guidelines pooled it, 390 citations in OpenAlex.
- MicroRNAs in Parkinson's disease: a systematic review and diagnostic accuracy meta-analysis.Scientific reports · 2023Pooled it
- Selective autophagy of intracellular organelles: recent research advances.Theranostics · 2021Pooled it
- LRPPRC: A Multifunctional Protein Involved in Energy Metabolism and Human Disease.Frontiers in physiology · 2019Pooled it
- Homocysteine and mitophagy in diabetic retinopathy: unraveling the underlying molecular crosstalk.Endocrine · 2026Review
- Repurposing Anticancer Drugs in Parkinson's Treatment: Molecular Pathways Driving Neuroprotection and Therapeutic Advancement.Molecular neurobiology · 2026Review
- Pseudomonas aeruginosa Impairs Mitochondrial Function During Infection of Corneal Epithelial Cells.Investigative ophthalmology & visual science · 2026Article
- Review
- Mitochondrial Quality Control and Pathogenic Signaling Networks in Parkinson's Disease.Current issues in molecular biology · 2026Review
- Inhibition of autophagy increases head and neck cancer sensitivity to cetuximab and radiation therapy.Scientific reports · 2026Article
- Body Fluid-based Biomarkers for Cognitive Impairment in Parkinson's Disease.Annals of neurosciences · 2026Review
- Parkin deficiency impairs female fertility, oocyte development, fertilization and mitochondrial function in mice.npj aging · 2026Article
- Article
- From mitochondrial zonation to immune dysregulation: a mechanistic axis in diabetic cardiomyopathy.Frontiers in cardiovascular medicine · 2026Review
- UBC/UBA52 silencing restores PINK1-Parkin-mediated mitochondrial autophagy in allergic rhinitis.PloS one · 2026Article
- Contrasting roles of autophagy in cellular prion infection.Autophagy · 2025Article
- The Ubiquitin-Proteasome System in Brain Disorders: Pathogenic Pathways, Post-Translational Tweaks, and Therapeutic Frontiers.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Review
- Mitophagy mitigates mitochondrial fatty acid β-oxidation deficient cardiomyopathy.Nature communications · 2025Article
- High fat diet (HFD) induced hepatic lipogenic metabolism and lipotoxicity via Parkin-dependent mitophagy and Errα signal of Pelteobagrus fulvidraco.Journal of animal science and biotechnology · 2025Article
- Targeting Autophagy for Pituitary Tumors.Cancers · 2025Review
- Article
166 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Two Parkinson's disease (PD)-associated proteins, the mitochondrial kinase PINK1 and the E3-ubiquitin (Ub) ligase PARKIN, are central to mitochondrial quality control. In this pathway, PINK1 accumulates on defective mitochondria, eliciting the translocation of PARKIN from the cytosol to mediate the clearance of damaged mitochondria via autophagy (mitophagy). Throughout the different stages of mitophagy, post-translational modifications (PTMs) are critical for the regulation of PINK1 and PARKIN activity and function. Indeed, activation and recruitment of PARKIN onto damaged mitochondria involves PINK1-mediated phosphorylation of both PARKIN and Ub. Through a stepwise cascade, PARKIN is converted from an autoinhibited enzyme into an active phospho-Ub-dependent E3 ligase. Upon activation, PARKIN ubiquitinates itself in concert with many different mitochondrial substrates. The Ub conjugates attached to these substrates can in turn be phosphorylated by PINK1, which triggers further cycles of PARKIN recruitment and activation. This feed-forward amplification loop regulates both PARKIN activity and mitophagy. However, the precise steps and sequence of PTMs in this cascade are only now being uncovered. For instance, the Ub conjugates assembled by PARKIN consist predominantly of noncanonical K6-linked Ub chains. Moreover, these modifications are reversible and can be disassembled by deubiquitinating enzymes (DUBs), including Ub-specific protease 8 (USP8), USP15, and USP30. However, PINK1-mediated phosphorylation of Ub can impede the activity of these DUBs, adding a new layer of complexity to the regulation of PARKIN-mediated mitophagy by PTMs. It is therefore evident that further insight into how PTMs regulate the PINK1-PARKIN pathway will be critical for our understanding of mitochondrial quality control.
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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.