ArticleThe Journal of biological chemistry
Insights into the catalytic properties of the mitochondrial rhomboid protease PARL.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 35 citations in OpenAlex.
- Targeting the Membrane-Embedded Rhomboid Protease GlpG: A Multimodal Strategy for Inhibitor Discovery and Mechanistic Insight.Angewandte Chemie (International ed. in English) · 2026Article
- Integrative Transcriptomic Analysis Identifies Novel Mitochondrial Gene Targets in Parkinson's Disease.Molecular neurobiology · 2026Article
- Enhancing schistosomiasis drug discovery approaches with optimized proteasome substrates.Protein science : a publication of the Protein Society · 2025Article
- The Role of Cardiolipin in Brain Bioenergetics, Neuroinflammation, and Neurodegeneration.Molecular neurobiology · 2025Review
- Transmembrane Parkinson's disease mutation of PINK1 leads to altered mitochondrial anchoring.The Journal of biological chemistry · 2025Article
- 4-Oxo-β-lactams as Covalent Inhibitors of the Mitochondrial Intramembrane Protease PARL.ACS medicinal chemistry letters · 2024Article
- AnbioRxiv : the preprint server for biology · 2024Article
- 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
- Chemical Blockage of the Mitochondrial Rhomboid Protease PARL by Novel Ketoamide Inhibitors Reveals Its Role in PINK1/Parkin-Dependent Mitophagy.Journal of medicinal chemistry · 2023Article
- Multiplex substrate profiling by mass spectrometry for proteases.Methods in enzymology · 2023Article
- MTSviewer: A database to visualize mitochondrial targeting sequences, cleavage sites, and mutations on protein structures.PloS one · 2023Article
- Mitochondrial Processing Peptidases-Structure, Function and the Role in Human Diseases.International journal of molecular sciences · 2022Review
- Plasma-derived phosphoglycerate mutase 5 as a biomarker for Parkinson's disease.Frontiers in aging neuroscience · 2022Article
- A novel role of KEAP1/PGAM5 complex: ROS sensor for inducing mitophagy.Redox biology · 2021Article
- Differential Neuropeptidomes of Dense Core Secretory Vesicles (DCSV) Produced at Intravesicular and Extracellular pH Conditions by Proteolytic Processing.ACS chemical neuroscience · 2021Article
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The rhomboid protease PARL is a critical regulator of mitochondrial homeostasis through its cleavage of substrates such as PINK1, PGAM5, and Smac/Diablo, which have crucial roles in mitochondrial quality control and apoptosis. However, the catalytic properties of PARL, including the effect of lipids on the protease, have never been characterized in vitro. To address this, we isolated human PARL expressed in yeast and used FRET-based kinetic assays to measure proteolytic activity in vitro. We show that PARL activity in detergent is enhanced by cardiolipin, a lipid enriched in the mitochondrial inner membrane. Significantly higher turnover rates were observed for PARL reconstituted in proteoliposomes, with Smac/Diablo being cleaved most rapidly at a rate of 1 min
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