ArticleThe EMBO journal2019
Parkin inhibits BAK and BAX apoptotic function by distinct mechanisms during mitophagy.
Article in The EMBO journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 110 citations in OpenAlex.
- PTEN-L inhibits mitophagy and GSDME-dependent pyroptosis via Parkin dephosphorylation.EMBO reports · 2026Article
- Mitochondria as the Hub of Apoptosis: A Comprehensive Insight From Mitochondria to Interactions With Other Organelles.MedComm · 2026Review
- The Protective Role of Selenium Against Thyroid Injury in Pigs: Involvement of PINK1/Parkin-Mediated Mitophagy and Apoptosis Regulation.Biological trace element research · 2026Article
- Network Topology and Interactomic Analysis Reveal the Regulatory Framework of the Humanin Protein Family (MTRNR2Lx Class).Biomolecules · 2026Article
- The central cholinergic system as a therapeutic target in Parkinson's disease.Journal of Parkinson's disease · 2026Review
- WWP2 underlies ROS-induced granulosa cell apoptosis by promoting ubiquitination of BAK in polycystic ovary syndrome.Cell death & disease · 2026Article
- Novel insight into PINK1/parkin-associated autophagy implicated in Parkinson disease.Translational neuroscience · 2026Review
- Intranasal delivery route for neurodegenerative diseases: recent insights and future directions.Drug delivery and translational research · 2026Review
- Okanin Attenuates Mitochondrial Dysfunction and Apoptosis in UVA-Induced HaCaT Cells by Mitophagy Through SIRT3 Pathway.Antioxidants (Basel, Switzerland) · 2025Article
- A new era in cancer therapy: targeting the Proteasome-Bcl-2 axis.Journal of experimental & clinical cancer research : CR · 2025Review
- Engineering a cell-based orthogonal ubiquitin transfer cascade for profiling the substrates of RBR E3 Parkin.iScience · 2025Article
- Mitochondrial Dysfunction is a Crucial Immune Checkpoint for Neuroinflammation and Neurodegeneration: mtDAMPs in Focus.Molecular neurobiology · 2025Review
- Repurposing chlorpromazine for the treatment of triple-negative breast cancer growth and metastasis based on modulation of mitochondria-mediated apoptosis and autophagy/mitophagy.British journal of cancer · 2025Article
- Mitochondria - the CEO of the cell.Journal of cell science · 2025Review
- Important regulatory role of mitophagy in diabetic microvascular complications.Journal of translational medicine · 2025Review
- Role of mitophagy in breast cancer: mitophagy-apoptosis balance and reactive oxygen species play determining role.Frontiers in physiology · 2025Review
- Cell-free mitochondrial DNA as a pro-inflammatory agent in blood circulation: mechanisms, therapeutic implications, and clinical challenges in immune dysregulation.Frontiers in immunology · 2025Review
- Activation of AMPK/OPA1 pathway alleviates traumatic brain damage by regulating mitophagy.Acta cirurgica brasileira · 2025Article
- Mitochondria and cell death.Nature cell biology · 2024Review
- Oxygen vacancy-engineered cerium oxide mediated by copper-platinum exhibit enhanced SOD/CAT-mimicking activities to regulate the microenvironment for osteoarthritis therapy.Journal of nanobiotechnology · 2024Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The E3 ubiquitin ligase Parkin is a key effector of the removal of damaged mitochondria by mitophagy. Parkin determines cell fate in response to mitochondrial damage, with its loss promoting early onset Parkinson's disease and potentially also cancer progression. Controlling a cell's apoptotic response is essential to co-ordinate the removal of damaged mitochondria. We report that following mitochondrial damage-induced mitophagy, Parkin directly ubiquitinates the apoptotic effector protein BAK at a conserved lysine in its hydrophobic groove, a region that is crucial for BAK activation by BH3-only proteins and its homo-dimerisation during apoptosis. Ubiquitination inhibited BAK activity by impairing its activation and the formation of lethal BAK oligomers. Parkin also suppresses BAX-mediated apoptosis, but in the absence of BAX ubiquitination suggesting an indirect mechanism. In addition, we find that BAK-dependent mitochondrial outer membrane permeabilisation during apoptosis promotes PINK1-dependent Parkin activation. Hence, we propose that Parkin directly inhibits BAK to suppress errant apoptosis, thereby allowing the effective clearance of damaged mitochondria, but also promotes clearance of apoptotic mitochondria to limit their potential pro-inflammatory effect.
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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.