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Updated: Jan 20, 2026
Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
Published on: August 7, 2018
Necroptosis signaling in liver diseases: An update
Waqar Khalid Saeed1, Dae Won Jun1, Kiseok Jang2
1Department of Internal Medicine, Hanyang University School of Medicine, Seoul, South Korea.
Abstract:
The apoptosis alternate cell death pathways are extensively studied in recent years and their significance has been well recognized. With identification of newer cell death pathways, the therapeutic opportunities to modulate cell death have indeed further extended. Necroptosis, among other apoptosis alternate pathways, has been immensely studied recently in different hepatic disease models. Receptor-interacting protein 1 (RIPK1), RIPK3 and mixed lineage kinase domain like (MLKL) seemed to be the key players to mediate necroptosis pathway. Initially, necroptosis seemed to be following the typical pathway. But recently diverse pathways and outcomes have been observed. With recent studies reporting diverse outcomes, the necroptosis signalling has become a lot more interesting and intricate. The typical RIPK1 signalling followed by RIPK3 and MLKL might not always be strictly followed. Although, necroptosis signalling has been intensively investigated in various disease conditions; however, there is still a need to further elaborate and understand the unique scaffolding and kinase properties and other signalling interactions of necroptosis signalling molecules.
Insights
Necroptosis, an alternate cell death pathway involving RIPK1, RIPK3, and MLKL, is increasingly recognized for its therapeutic potential in liver diseases. Recent studies reveal complex signaling, highlighting the need for deeper understanding of its molecular interactions.
Area of Science:
- Cellular Biology
- Molecular Medicine
- Pathology
Background:
- Apoptosis alternate cell death pathways are gaining recognition for their therapeutic implications.
- Necroptosis, a key alternate pathway, is extensively studied in hepatic disease models.
- Receptor-interacting protein 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like (MLKL) are central to necroptosis.
Purpose of the Study:
- To explore the intricate and diverse signaling pathways of necroptosis.
- To highlight the need for further understanding of necroptosis signaling molecules' properties.
- To underscore the therapeutic opportunities in modulating cell death.
Main Methods:
- Review of recent studies on necroptosis signaling.
- Analysis of the roles of RIPK1, RIPK3, and MLKL in hepatic disease models.
- Investigation of diverse signaling outcomes beyond the typical pathway.
Main Results:
- Necroptosis signaling is more complex and diverse than initially thought.
- The canonical RIPK1-RIPK3-MLKL pathway is not always strictly followed.
- Varied signaling interactions and outcomes are observed in different contexts.
Conclusions:
- Necroptosis signaling pathways are intricate and multifaceted.
- Further research is needed to elucidate the unique scaffolding and kinase properties of necroptosis molecules.
- Understanding these complexities can extend therapeutic strategies for cell death modulation.
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