Abstract: The fumigant phosphine has been widely used in protecting stored products against insect pests for over 60 years. However, the long-term and improper application of phosphine has led to extensive phosphine resistance among stored product pests. Knowledge of the mechanisms of phosphine toxicology can provide ideas for the study of the mechanisms of phosphine resistance. Although it has been accepted that phosphine causes death of insect pests by disruption of the nerve conduction, suppression of energy metabolism, and destruction of the redox system, recent studies have revealed that the main lethal mechanisms involve inhibiting the energy production, and disturbing redox system to increase oxidative damage. Earlier studies demonstrated that the mechanisms of phosphine resistance mainly included active exclusion of phosphine, protective narcosis, and upregulation of detoxification enzyme activities. In recent years, with the application of genomics, proteomics, and metabolomics, some novel resistance mechanisms, such as penetration resistance, decreased sensitivity of the target of phosphine, and reprogrammed energy metabolism, have been proposed. Increasing researches supported that strong phosphine resistance should be mainly attributed to mutations of the target dihydrolipoamide dehydrogenase and upregulation of antioxidase and detoxification enzyme activities, while reprogrammed energy metabolism is a possible strategy adopted to counteract the negative influence of phosphine during the early stage of resistance formation. Application of gene introgression in the study of fitness costs associated with phosphine resistance mutations facilitates precisely predicting the evolution direction of resistance mutations. Knowledge of the mechanisms of phosphine resistance and the evolutionary potential of resistance mutations not only helps understand pesticide resistance development and biological evolution, but also provides insights into the monitoring and management of phosphine resistance.

Key words: Phosphine, pesticide resistance, dihydrolipoamide dehydrogenase, redox, energy metabolism