ArticleNature cell biology2019
The AMPK-Parkin axis negatively regulates necroptosis and tumorigenesis by inhibiting the necrosome.
Article in Nature cell biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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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.
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Who cites it
105 citing papers in PubMed, 170 citations in OpenAlex.
- E3 ubiquitin ligase-mediated necroptosis: regulatory mechanisms and therapeutic implication in cancer.Molecular biology reports · 2026Review
- Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026Review
- Molecular mechanisms underlying FCCP-induced mitophagy in human airway smooth muscle cells.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- AMPK as a central regulator of necroptosis: mechanistic insights and therapeutic implications.Journal of physiology and biochemistry · 2026Review
- Interaction between p-AMPK and RIPK3 reveals a mechanism by which AdipoAI suppresses necroptosis to attenuate periodontitis.Journal of translational medicine · 2026Article
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- The c-Abl-RIPK3 Axis Drives Mitochondrial Dysfunction and Impaired Mitophagy in Gaucher Disease Models.Antioxidants (Basel, Switzerland) · 2026Article
- Targeting ubiquitin-specific peptidase 22 in solid tumours: from ubiquitination to immunotherapy.Frontiers in cell and developmental biology · 2026Review
- Targeting necroptosis: how does exercise protect against metabolic dysfunction-associated fatty liver disease?Frontiers in physiology · 2026Review
- Focus on necroptosis: its role in the pathogenesis and therapeutic potential of osteoarthritis.Frontiers in immunology · 2026Review
- Neuroinflammation demonstrated byAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- The AMPK Pathway: Molecular Rejuvenation of Metabolism and Mitochondria.Annual review of cell and developmental biology · 2025Review
- Molecular regulation of mitophagy signaling in tumor microenvironment and its targeting for cancer therapy.Cytokine & growth factor reviews · 2025Review
- Silicon-rhodamine-enabled identification for near-infrared light controlled proximity labeling in vitro and in vivo.Nature communications · 2025Article
- Canonical and alternate mechanisms that regulate ubiquitylation by the E3 ligase parkin.Biochemical Society transactions · 2025Review
- Opposing regulation of the K63-linked polyubiquitination of RIPK3 by SMURF1 and USP5 in necroptosis.Nature communications · 2025Article
- Inhibition of UBE2C Promotes Parkin-Mediated K63-Linked Ubiquitination of TOP2A to Induce Senescence and Increase Sensitivity of Doxorubicin in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Necroptosis in cancer: insight from epigenetic, post-transcriptional and post-translational modifications.Journal of hematology & oncology · 2025Review
- Engineering a cell-based orthogonal ubiquitin transfer cascade for profiling the substrates of RBR E3 Parkin.iScience · 2025Article
- Cell death and cancer: Metabolic interconnections.Cell reports · 2025Review
45 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 11 institutions in 3 countries.
Funding
Abstract
The receptor-interacting serine/threonine-protein kinases RIPK1 and RIPK3 play important roles in necroptosis that are closely linked to the inflammatory response. Although the activation of necroptosis is well characterized, the mechanism that tunes down necroptosis is largely unknown. Here we find that Parkin (also known as PARK2), an E3 ubiquitin ligase implicated in Parkinson's disease and as a tumour suppressor, regulates necroptosis and inflammation by regulating necrosome formation. Parkin prevents the formation of the RIPK1-RIPK3 complex by promoting polyubiquitination of RIPK3. Parkin is phosphorylated and activated by the cellular energy sensor AMP-activated protein kinase (AMPK). Parkin deficiency potentiates the RIPK1-RIPK3 interaction, RIPK3 phosphorylation and necroptosis. Parkin deficiency enhances inflammation and inflammation-associated tumorigenesis. These findings demonstrate that the AMPK-Parkin axis negatively regulates necroptosis by inhibiting RIPK1-RIPK3 complex formation; this regulation may serve as an important mechanism to fine-tune necroptosis and inflammation.
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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.