Necroptosis molecular mechanisms: Recent findings regarding novel necroptosis regulators

Jinho Seo, Young Woo Nam, Seongmi Kim, Doo Byoung Oh, Jaewhan Song

Research output: Contribution to journalReview articlepeer-review

65 Citations (Scopus)


Necroptosis is a form of programmed necrosis that is mediated by various cytokines and pattern recognition receptors (PRRs). Cells dying by necroptosis show necrotic phenotypes, including swelling and membrane rupture, and release damage-associated molecular patterns (DAMPs), inflammatory cytokines, and chemokines, thereby mediating extreme inflammatory responses. Studies on gene knockout or necroptosis-specific inhibitor treatment in animal models have provided extensive evidence regarding the important roles of necroptosis in inflammatory diseases. The necroptosis signaling pathway is primarily modulated by activation of receptor-interacting protein kinase 3 (RIPK3), which phosphorylates mixed-lineage kinase domain-like protein (MLKL), mediating MLKL oligomerization. In the necroptosis process, these proteins are fine-tuned by posttranslational regulation via phosphorylation, ubiquitination, glycosylation, and protein–protein interactions. Herein, we review recent findings on the molecular regulatory mechanisms of necroptosis.

Original languageEnglish
Pages (from-to)1007-1017
Number of pages11
JournalExperimental and Molecular Medicine
Issue number6
Publication statusPublished - 2021 Jun

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation of Korea [NRF-2015R1A3A2066581 and 2020R1C1C1006833], Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program, and BK21 PLUS program. All figures were created with

Publisher Copyright:
© 2021, The Author(s).

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry


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