Cuproptosis Cell Death Molecular Events and Pathways to Liver Disease

Chronic liver disease ranks as the 11th leading cause of death worldwide, while hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality, representing a substantial risk to public health. Over the past few decades, the global landscape of chronic liver diseases, including hepatitis, metabolic dysfunction-associated steatotic liver disease (MASLD), liver fibrosis, and HCC, has undergone substantial changes. Copper, a vital trace element for human health, is predominantly regulated by the liver. Both copper deficiency and excess can lead to cellular damage and liver dysfunction. Copper deposition is a genetic process of copper-dependent cell death associated with mitochondrial respiration, which is associated with cardiovascular disease and IBD. However, the roles of copper overload and cuproptosis in liver disease remain largely underexplored. This article examines recent studies on copper metabolism and cuproptosis in chronic liver disease, investigating the potential of targeting copper ions as a therapeutic approach. The objective is to offer insights and guidance for future investigations in this developing field of study.