ArticlePloS one2016
Mitochondrial Protein PGAM5 Regulates Mitophagic Protection against Cell Necroptosis.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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
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Who cites it
90 citing papers in PubMed, 156 citations in OpenAlex.
- Mitochondrial Dysfunction at the Crossroads of Necroptosis: Mechanisms, Molecular Mediators, and Therapeutic Opportunities.Journal of cellular and molecular medicine · 2026Review
- Post-translational modifications of mitochondrion-related proteins: integrative orchestrators of cell fate networks in cardiovascular disease.Cell communication and signaling : CCS · 2026Review
- Targeting Ferroptosis and Necroptosis to Treat Stroke.Neurochemical research · 2026Review
- Amyloid precursor protein interacts with the mitochondrial phosphatase PGAM5 and regulates mitochondrial respiration.bioRxiv : the preprint server for biology · 2026Article
- Procyanidin Capsules Combat ALF by Restoring Mitochondrial Homeostasis and Inhibiting Necroptosis via the PGAM5/DRP1/PINK1 Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Molecular and Cellular Mechanisms of Myocardial Ischemia and Reperfusion Injury: A Narrative Review.Cells · 2026Review
- Trigger Points of Necroptosis (RIPK1, RIPK3, and MLKL)-Promising Horizon or Blind Alley in Therapy of Colorectal Cancer?International journal of molecular sciences · 2025Review
- Polymorphisms in Necroptosis Pathway Genes: Novel Prognostic Markers for Multiple Myeloma Treatment Outcomes.International journal of molecular sciences · 2025Article
- Mitophagy is induced in human engineered heart tissue after simulated ischemia and reperfusion.Journal of cell science · 2025Article
- Phosphoglycerate Mutase 5 Is Important Mediator for Instigating Arterial Lipid Accumulation and Aggravating Atherosclerosis.JACC. Basic to translational science · 2025Article
- Article
- Transmembrane Parkinson's disease mutation of PINK1 leads to altered mitochondrial anchoring.The Journal of biological chemistry · 2025Article
- Neuronal Injury after Ischemic Stroke: Mechanisms of Crosstalk Involving Necroptosis.Journal of molecular neuroscience : MN · 2025Review
- The multifaceted role of autophagy and mitophagy in cardiovascular health and disease.Autophagy reports · 2025Review
- Mechanisms and Therapeutic Potential of Multiple Forms of Cell Death in Myocardial Ischemia-Reperfusion Injury.International journal of molecular sciences · 2024Review
- Identification and validation of protein biomarkers for predicting gastrointestinal stromal tumor recurrence.Computational and structural biotechnology journal · 2024Article
- M1 macrophage-derived exosomes alleviate leukemia by causing mitochondrial dysfunction.Annals of hematology · 2024Article
- Neuroinflammation in Age-Related Neurodegenerative Diseases: Role of Mitochondrial Oxidative Stress.Antioxidants (Basel, Switzerland) · 2024Review
- Investigating the interplay between mitophagy and diabetic neuropathy: Uncovering the hidden secrets of the disease pathology.Pharmacological research · 2024Review
- Therapeutic Strategies Targeting Mitochondrial Dysfunction in Sepsis-induced Cardiomyopathy.Cardiovascular drugs and therapy · 2024Review
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
Necroptosis as a molecular program, rather than simply incidental cell death, was established by elucidating the roles of receptor interacting protein (RIP) kinases 1 and 3, along with their downstream partner, mixed lineage kinase-like domain protein (MLKL). Previous studies suggested that phosphoglycerate mutase family member 5 (PGAM5), a mitochondrial protein that associates with RIP1/RIP3/MLKL complex, promotes necroptosis. We have generated mice deficient in the pgam5 gene and surprisingly found PGAM5-deficiency exacerbated rather than reduced necroptosis in response to multiple in vitro and in vivo necroptotic stimuli, including ischemic reperfusion injury (I/R) in the heart and brain. Electron microscopy, biochemical, and confocal analysis revealed that PGAM5 is indispensable for the process of PINK1 dependent mitophagy which antagonizes necroptosis. The loss of PGAM5/PINK1 mediated mitophagy causes the accumulation of abnormal mitochondria, leading to the overproduction of reactive oxygen species (ROS) that worsen necroptosis. Our results revise the former proposal that PGAM5 acts downstream of RIP1/RIP3 to mediate necroptosis. Instead, PGAM5 protects cells from necroptosis by independently promoting mitophagy. PGAM5 promotion of mitophagy may represent a therapeutic target for stroke, myocardial infarction and other diseases caused by oxidative damage and necroptosis.
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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.