The role of RIPK3 in liver mitochondria bioenergetics and function

Abstract

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.

Keywords: NAFLD; NASH; RIPK3; mitochondria; necroptosis.