RIP3 and MLKL regulate ER stress in alcohol-associated liver disease and pharmacological ER stress models: Insights beyond necroptosis.

ABSTRACT:

Background & aims

Endoplasmic reticulum (ER) stress is an important contributor to liver disease progression, including alcohol-associated liver disease. Although receptor-interacting protein kinase-3 (RIP3) and mixed lineage kinase domain-like pseudokinase (MLKL) are known for their roles in necroptosis, emerging evidence highlights their non-canonical functions in metabolic regulation and cellular-stress responses. However, their specific role in regulating hepatic ER stress remains unclear. This study investigates how RIP3 and MLKL regulate ER stress pathways during chronic ethanol exposure and pharmacological ER stress induction.

Methods

Rip3 ^-/- , Rip3 ^K51A/K51A , and Mlkl ^-/- mice alongside wild

SUBMITTER: Arya RK 

PROVIDER: S-EPMC12857340 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature