Carnitine Shuttle and Ferroptosis in Cancer

Ferroptosis is a unique type of regulated cell death characterized by iron-dependent lipid peroxidation, and it has emerged as a promising therapeutic target in cancer treatment. The carnitine shuttle system, which is crucial for transporting fatty acids across the mitochondrial membrane, has been identified as a key regulator of ferroptosis in cancer cells. This review investigates the intricate relationship between the carnitine shuttle and ferroptosis in cancer. We provide a comprehensive review of how the components of the carnitine system, including carnitine palmitoyltransferase 1A (CPT1A), carnitine palmitoyltransferase 2, and carnitine-acylcarnitine translocase, influence cellular redox homeostasis, fatty acid metabolism, and interact with proteins related to ferroptosis sensitivity. We discuss therapeutic implications of targeting the carnitine shuttle system, particularly CPT1A, to overcome ferroptosis resistance and enhance the efficacy of immunotherapy in various cancer types. This review offers further research directions, highlighting the crosstalk between the carnitine shuttle, ferroptosis, and various signaling pathways involved in cancer progression to improve cancer treatment.