Targeting Ferroptosis and Cuproptosis for Antimicrobial Control in Postharvest Preservation

Abstract

Spoilage and pathogenic microorganisms cause significant economic losses and food safety issues globally, driving the need for novel antimicrobial strategies beyond conventional methods. This review explores the potential of targeting two metal-dependent regulated cell death pathways, ferroptosis and cuproptosis, for precision antimicrobial intervention in postharvest preservation. Ferroptosis is driven by iron-dependent lipid peroxidation, while cuproptosis is characterized by copper-induced aggregation of metabolic proteins and subsequent proteotoxic stress. We delineate their molecular mechanisms and highlight their operational presence in key bacterial and fungal pathogens. The review critically examines pioneering applications, such as iron-loaded biodegradable films and copper-based nanocomposites, which exploit these pathways to control spoilage microorganisms on various produce, thereby maintaining sensory quality and extending shelf life. We also propose that the co-induction of ferroptosis and cuproptosis overwhelms microbial defenses by disrupting interconnected iron and copper homeostasis, amplifying oxidative stress, and impeding resistance development. Despite the promise, translating this paradigm into practical applications requires overcoming challenges related to targeted delivery, biosafety, and phytotoxicity. We conclude that leveraging these mechanistically distinct pathways, particularly through synergistic strategies, represents a transformative frontier for sustainable, efficient, and resistance-resilient solutions to reduce postharvest losses and enhance food security.