Distinct Types of Cell Death and Implications in Liver Diseases: An Overview of Mechanisms and Application

Abstract

Cell death is associated with a variety of liver diseases, and hepatocyte death is a core factor in the occurrence and progression of liver diseases. In recent years, new cell death modes have been identified, and certain biomarkers have been detected in the circulation during various cell death modes that mediate liver injury. In this review, cell death modes associated with liver diseases are summarized, including some cell death modes that have emerged in recent years. We described the mechanisms associated with liver diseases and summarized recent applications of targeting cell death in liver diseases. It provides new ideas for the diagnosis and treatment of liver diseases. In addition, multiple cell death modes can contribute to the same liver disease. Different cell death modes are not isolated, and they interact with each other in liver diseases. Future studies may focus on exploring the regulation between various cell death response pathways in liver diseases.

Keywords: Application; Cell death; Hepatocytes; Liver diseases.

Fig. 1. Mechanism of apoptosis, necrosis, necroptosis and autophagy.

FADD, fas-associated protein; Fas-L, fas ligand; JNK, cJun-N-terminal Kinase; MLKL, mixed lineage kinase domain protein; MPT, mitochondrial permeability transition; RIPK1, receptor interacting protein kinases 1; RIPK3, receptor interacting protein kinases 3; TNF, tumor necrosis factor; TRADD, TNFR1-associated death domain protein.

Fig. 2. Mechanisms of ferroptosis, pyroptosis, NETosis and cuproptosis.

ASC, apoptosis-associated speck-like protein; CoQ, coenzyme Q;DAMP, damage-associated molecular modes; DLAT, dihydrolipoic acid s-acetyltransferase; FDX1, iron oxidation reduction protein 1; FSP1, ferroptosis inhibitory protein 1; GPX4, glutathione peroxidase 4; GSDMD, gasdermin D; GSH, glutathione; IL, interleukin; LPS, lipopolysaccharide; PAMP, pathogen-associated molecular modes; PMA, phorbol 12-myristate 13-acetate; ROS, reactive oxygen species; SLC3A2, solute carrier family 3 member 2; SLC7A11, solute carrier family 7 member 11; TAC, tricarboxylic acid cycle.