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The role of RIPK3 in liver mitochondria bioenergetics and function
Tawhidul Islam1, Marta B Afonso1, Cecília M P Rodrigues1
1Faculty of Pharmacy, Research Institute for Medicines (iMed.ULisboa), Universidade de Lisboa, Lisbon, Portugal.
Background:
Receptor-interacting protein kinase 3 (RIPK3) is a key player of regulated necrosis or necroptosis, an inflammatory form of cell death possibly governing outcomes in chronic liver diseases, such as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.
Methods:
This narrative review is based on literature search using PubMed.
Results:
RIPK3 activation depends on post-transcriptional modifications, including phosphorylation, hence coordinating the assembly of macromolecular death complex named 'necrosome', which may also involve diverse mitochondrial components. Curiously, recent studies suggested a potential link between RIPK3 and mitochondrial bioenergetics. RIPK3 can modulate mitochondrial function and quality through the regulation of mitochondrial reactive oxygen species production, sequestration of metabolic enzymes and resident mitochondrial proteins, activity of mitochondrial respiratory chain complexes, mitochondrial biogenesis and fatty acid oxidation.
Conclusions:
Since mitochondrial dysfunction and RIPK3-mediated necroptosis are intimately involved in chronic liver disease pathogenesis, understanding the role of RIPK3 in mitochondrial bioenergetics and its potential translational application are of great interest.
Insights
Receptor-interacting protein kinase 3 (RIPK3) regulates necroptosis and impacts mitochondrial function. Understanding RIPK3
Area of Science:
- Cellular Biology
- Molecular Biology
- Hepatology
Background:
- Receptor-interacting protein kinase 3 (RIPK3) is central to necroptosis, an inflammatory cell death pathway.
- Necroptosis plays a role in chronic liver diseases like nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.
Purpose of the Study:
- To review the literature on the role of RIPK3 in mitochondrial bioenergetics.
- To explore the potential translational applications of targeting RIPK3 in liver disease.
Main Methods:
- This study is a narrative review based on a PubMed literature search.
Main Results:
- RIPK3 activation involves post-transcriptional modifications and forms the necrosome complex, potentially including mitochondrial components.
- RIPK3 influences mitochondrial function by regulating reactive oxygen species, metabolic enzymes, respiratory chain activity, biogenesis, and fatty acid oxidation.
Conclusions:
- Mitochondrial dysfunction and RIPK3-mediated necroptosis are implicated in chronic liver disease pathogenesis.
- Further understanding of RIPK3's role in mitochondrial bioenergetics is crucial for potential therapeutic strategies.
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