The PANoptosome: A Deadly Protein Complex Driving Pyroptosis, Apoptosis, and Necroptosis (PANoptosis)
Open accessAbstract
Programmed cell death is regulated by evolutionarily conserved pathways that play critical roles in development and the immune response. A newly recognized pathway for proinflammatory programmed cell death called PANoptosis is controlled by a recently identified cytoplasmic multimeric protein complex named the PANoptosome. The PANoptosome can engage, in parallel, three key modes of programmed cell death-pyroptosis, apoptosis, and necroptosis. The PANoptosome components have been implicated in a wide array of human diseases including autoinflammatory diseases, neurodegenerative diseases, cancer, microbial infections, and metabolic diseases. Here, we review putative components of the PANoptosome and present a phylogenetic analysis of their molecular domains and interaction motifs that support complex assembly. We also discuss genetic data that suggest PANoptosis is coordinated by scaffolding and catalytic functions of the complex components and propose mechanistic models for PANoptosome assembly. Overall, this review presents potential mechanisms governing PANoptosis based on evolutionary analysis of the PANoptosome components.
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The PANoptosome includes various molecules necessary for the activation of downstream programmed cell death (PCD) effectors such as GSDMD, GSDME, CASP3/7, and MLKL.
“This complex includes various molecules necessary for the activation of downstream programmed cell death (PCD) effectors such as GSDMD, GSDME, CASP3/7, and MLKL (Fig. 4).”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [274]
The Introduction and Components of the PANoptosome sections say the complex contains molecules involved in pyroptosis, apoptosis, and necroptosis; the Introduction identifies gasdermin-family members, executioner caspases, and MLKL as downstream effectors of those pathways (page unavailable). The copy does not specifically establish activation of GSDMD, GSDME, or CASP3/7 by the PANoptosome, so the named list is more specific than the source supports. (LLM, conf=0.85)
Experimental — accuracy not yet measuredCytokines or PAMPs trigger the assembly of a multiprotein complex called the PANoptosome.
“Cytokines or PAMPs trigger the assembly of a multiprotein complex called the PANoptosome.”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [274]
The Components of the PANoptosome section identifies putative PAMP sensors, and The Mechanism of PANoptosome Assembly Through Phylogenetic Analysis proposes that sensing influenza viral material initiates assembly of the multiprotein complex. The paper does not establish cytokines as direct triggers of PANoptosome assembly; Established Mechanisms of PANoptosis instead describes cytokines as downstream products of PANoptosis, although it notes a role for type I interferon signaling in influenza-induced cell death. No page numbers are available in our copy. (LLM, conf=0.83)
Experimental — accuracy not yet measuredPANoptosis is a united modality of inflammatory programmed cell death, accompanied by markers of apoptosis, necrosis, and pyroptosis pathways.
“PANoptosis, is a united modality of inflammatory programmed cell death, accompanied by markers of apoptosis, necrosis, and pyroptosis pathways.271–275”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [274]
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Karki, R., Sharma, B. R., Tuladhar, S., Williams, E. P., Zalduondo, L., Samir, P., Zheng, M., Sundaram, B., Banoth, B., Malireddi, R. K. S., et al. (2021) · Cell · doi:10.1016/j.cell.2020.11.025 · Cited by 1,734 · see citing works
Self-citationInflammation and aging: signaling pathways and intervention therapies
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Self-citationRIPK1 Distinctly Regulates <i>Yersinia</i>-Induced Inflammatory Cell Death, PANoptosis
Malireddi, R. K. S., Kesavardhana, S., Karki, R., Kancharana, B., Burton, A. R., & Kanneganti, T.-D. (2020) · ImmunoHorizons · doi:10.4049/immunohorizons.2000097 · Cited by 224 · see citing works
Self-citation
- Authors
- Samir, P., Malireddi, R. K. S., & Kanneganti, T.-D.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Corresponding author
- Kanneganti, Thirumala-Devi
- Venue
- Frontiers in Cellular and Infection Microbiology
- Publisher
- Frontiers Media SA
- Published
- 2020-06-03
- Volume
- 10
- Pages
- 238-238
- ISSN
- 2235-2988 (ISSN-L)
- PMC
- PMC7283380
- OpenAlex
- W3034103545
- Cited by
- 557
- References
- 156
- Citations by year
- 2026: 110 · 2025: 140 · 2024: 113 · 2023: 76 · 2022: 64 · 2021: 28 · 2020: 26
- FWCI
- 4.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Cellular and Infection Microbiology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- American Lebanese Syrian Associated Charities
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- PANoptosome, PANoptosis, programmed cell death, pyroptosis, apoptosis, necroptosis, protein complex formation, phylogenetic analysis, protein interaction motifs, scaffold proteins, autoinflammatory disease, neurodegenerative diseases, cancer, microbial infection, metabolic disorders
- MeSH terms
- Pyroptosis, Necroptosis, Humans, Phylogeny, Apoptosis
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Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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