ArticleAutophagy2015
Intramembrane protease PARL defines a negative regulator of PINK1- and PARK2/Parkin-dependent mitophagy.
Article in Autophagy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 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.
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Who cites it
54 citing papers in PubMed, 3 syntheses or guidelines pooled it, 106 citations in OpenAlex.
- The Intersection of Mitophagy and Autism Spectrum Disorder: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- Mitophagy interacts with mitochondrial dynamics and biogenesis, acting as a double-edged sword in digestive cancer.iScience · 2026Review
- Transmembrane domain switching controls PINK1 import and fate in mitochondria.The EMBO journal · 2026Article
- Astrocytic Mitochondria Transplantation Rescues Neuron Loss and Dendritic Injuries in Acute Cerebral Ischemic Stroke Mouse Model by Flexibly Regulating Mitochondria Dynamics.Annals of neurology · 2026Article
- Targeting the Membrane-Embedded Rhomboid Protease GlpG: A Multimodal Strategy for Inhibitor Discovery and Mechanistic Insight.Angewandte Chemie (International ed. in English) · 2026Article
- Mapping the global research landscape of mitophagy in Parkinson's disease: a bibliometric and visualization analysis.Hereditas · 2025Article
- MicroRNAs and synaptic dysfunction in Parkinson's disease.Molecular therapy. Nucleic acids · 2025Review
- Holding Out for a Model: Rhomboid Superfamily in Vertebrate Development and Disease.Journal of cellular physiology · 2025Review
- NDUFB9 ameliorates CUMS-induced depression-like behavior by promoting mitophagy.Translational psychiatry · 2025Article
- Mitophagy mitigates mitochondrial fatty acid β-oxidation deficient cardiomyopathy.Nature communications · 2025Article
- Transmembrane Parkinson's disease mutation of PINK1 leads to altered mitochondrial anchoring.The Journal of biological chemistry · 2025Article
- Transcriptomic imputation of genetic risk variants uncovers novel whole-blood biomarkers of Parkinson's disease.NPJ Parkinson's disease · 2024Article
- The mitochondrial protease PARL is required for spermatogenesis.Communications biology · 2024Article
- Potential application of traditional Chinese medicine in age-related macular degeneration-focusing on mitophagy.Frontiers in pharmacology · 2024Review
- The role of mitophagy in metabolic diseases and its exercise intervention.Frontiers in physiology · 2024Review
- Disruption of Mitophagy Flux through the PARL-PINK1 Pathway by CHCHD10 Mutations or CHCHD10 Depletion.Cells · 2023Article
- Mitochondria in health, disease, and aging.Physiological reviews · 2023Review
- Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in PINK1 and PARK2/Parkin are a main risk factor for familial Parkinson disease. While the physiological mechanism of their activation is unclear, these proteins have been shown in tissue culture cells to serve as a key trigger for autophagy of depolarized mitochondria. Here we show that ablation of the mitochondrial rhomboid protease PARL leads to retrograde translocation of an intermembrane space-bridging PINK1 import intermediate. Subsequently, it is rerouted to the outer membrane in order to recruit PARK2, which phenocopies mitophagy induction by uncoupling agents. Consistent with a role of this retrograde translocation mechanism in neurodegenerative disease, we show that pathogenic PINK1 mutants which are not cleaved by PARL affect PINK1 kinase activity and the ability to induce PARK2-mediated mitophagy. Altogether we suggest that PARL is an important intrinsic player in mitochondrial quality control, a system substantially impaired in Parkinson disease as indicated by reduced removal of damaged mitochondria in affected patients.
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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.