ArticleJournal of immunology (Baltimore, Md. : 1950)2016
The Mitochondrial Phosphatase PGAM5 Is Dispensable for Necroptosis but Promotes Inflammasome Activation in Macrophages.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 117 citations in OpenAlex.
- Identifying AIM2 Circulating Methylation Levels as a Novel Diagnostic Biomarker for Rheumatoid Arthritis Using Targeted DNA Methylation Sequencing.Endocrine, metabolic & immune disorders drug targets · 2026Article
- Phosphoglycerate Mutase 5 Is Important Mediator for Instigating Arterial Lipid Accumulation and Aggravating Atherosclerosis.JACC. Basic to translational science · 2025Article
- Review
- The dual role of PGAM5 in inflammation.Experimental & molecular medicine · 2025Review
- PGAM5 Modulates Macrophage Polarization, Aggravating Inflammation in COPD via the NF-κB Pathway.International journal of chronic obstructive pulmonary disease · 2025Article
- The PGAM5-NEK7 interaction is a therapeutic target for NLRP3 inflammasome activation in colitis.Acta pharmaceutica Sinica. B · 2025Article
- The CaMK Family Differentially Promotes Necroptosis and Mouse Cardiac Graft Injury and Rejection.International journal of molecular sciences · 2024Article
- Targeted knockdown of PGAM5 in synovial macrophages efficiently alleviates osteoarthritis.Bone research · 2024Article
- The E3 ubiquitin ligase MARCH2 protects against myocardial ischemia-reperfusion injury through inhibiting pyroptosis via negative regulation of PGAM5/MAVS/NLRP3 axis.Cell discovery · 2024Article
- PGAM5 exacerbates acute renal injury by initiating mitochondria-dependent apoptosis by facilitating mitochondrial cytochrome c release.Acta pharmacologica Sinica · 2024Article
- Pgam5 aggravates hyperglycemia-induced myocardial dysfunction through disrupting Phb2-dependent mitochondrial dynamics.International journal of medical sciences · 2024Article
- Article
- Differential effects of PGAM5 knockout on high fat high fructose diet and methionine choline-deficient diet induced non-alcoholic steatohepatitis (NASH) in mice.Cell & bioscience · 2023Article
- The Interplay Between Autophagy and Regulated Necrosis.Antioxidants & redox signaling · 2023Review
- Pathophysiology of Spinal Cord Injury and Tissue Engineering Approach for Its Neuronal Regeneration: Current Status and Future Prospects.Advances in experimental medicine and biology · 2023Review
- Mitochondrial PGAM5-Drp1 signaling regulates the metabolic reprogramming of macrophages and regulates the induction of inflammatory responses.Frontiers in immunology · 2023Article
- Absent in melanoma 2 (AIM2) in rheumatoid arthritis: novel molecular insights and implications.Cellular & molecular biology letters · 2022Review
- Necroptosis Contributes to LPS-Induced Activation of the Hypothalamic-Pituitary-Adrenal Axis in a Piglet Model.International journal of molecular sciences · 2022Article
- Necroptosis in heart disease: Molecular mechanisms and therapeutic implications.Journal of molecular and cellular cardiology · 2022Review
- E3 ubiquitin ligase ring finger protein 5 protects against hepatic ischemia reperfusion injury by mediating phosphoglycerate mutase family member 5 ubiquitination.Hepatology (Baltimore, Md.) · 2022Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The cytokine IL-1β is intimately linked to many pathological inflammatory conditions. Mature IL-1β secretion requires cleavage by the inflammasome. Recent evidence indicates that many cell death signal adaptors have regulatory roles in inflammasome activity. These include the apoptosis inducers FADD and caspase 8, and the necroptosis kinases receptor interacting protein kinase 1 (RIPK1) and RIPK3. PGAM5 is a mitochondrial phosphatase that has been reported to function downstream of RIPK3 to promote necroptosis and IL-1β secretion. To interrogate the biological function of PGAM5, we generated Pgam5(-/-) mice. We found that Pgam5(-/-) mice were smaller compared with wild type littermates, and male Pgam5(-/-) mice were born at sub-Mendelian ratio. Despite these growth and survival defects, Pgam5(-/-) cells responded normally to multiple inducers of apoptosis and necroptosis. Rather, we found that PGAM5 is critical for IL-1β secretion in response to NLRP3 and AIM2 inflammasome agonists. Moreover, vesicular stomatosis virus-induced IL-1β secretion was impaired in Pgam5(-/-) bone marrow-derived macrophages, but not in Ripk3(-/-) bone marrow-derived dendritic cells, indicating that PGAM5 functions independent of RIPK3 to promote inflammasome activation. Mechanistically, PGAM5 promotes ASC polymerization, maintenance of mitochondrial integrity, and optimal reactive oxygen species production in response to inflammasome signals. Hence PGAM5 is a novel regulator of inflammasome and caspase 1 activity that functions independently of RIPK3.
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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.