Protein palmitoylation in hepatic diseases: Functional insights and therapeutic strategies
Ying Wang, Haoyuan Ma, Bowen Zhang, Sainan Li, Beijia Lu, Yingcheng Qi, Tingting Liu, Hua Wang, Xiaohong Kang, Yinming Liang, Eryan Kong, Liu Cao, Binhui Zhou
Abstract
• Protein palmitoylation plays a pivotal role in regulating liver disease pathophysiology, offering diagnostic and therapeutic potential. • Small molecule inhibitors targeting palmitoylation enzymes emerge as a new treatment for liver diseases. • Palmitoylation regulates immune responses in liver infections and tumors, potentially enhancing immunotherapy efficacy. Liver pathologies represent a spectrum of conditions ranging from fatty liver to the aggressive hepatocellular carcinoma (HCC), as well as parasitic infections, which collectively pose substantial global health challenges. S-palmitoylation (commonly referred to as palmitoylation), a post-translational modification (PTM) characterized by the covalent linkage of a 16-carbon palmitic acid (PA) chain to specific cysteine residues on target proteins, plays a pivotal role in diverse cellular functions and is intimately associated with the liver’s physiological and pathological states. This study aims to elucidate how protein palmitoylation affects liver disease pathophysiology and evaluates its potential as a target for diagnostic and therapeutic interventions. Recent studies have identified the key role of protein palmitoylation in regulating the development and progression of liver diseases. This review summarizes the intricate mechanisms by which protein palmitoylation modulates the pathophysiological processes of liver diseases and explores the potential of targeting protein palmitoylation modifications or the enzymes regulating this modification as prospective diagnostic biomarkers and therapeutic targets.