The mechanism underlying toxicity of a venom peptide against insects reveals how ants are master at disrupting membranes

Hymenopterans represent one of the most abundant groups of venomous organ-isms but remain little explored due to the difficult access to their venom. The development of proteo-transcriptomic allowed us to explore diversity of their toxins offering interesting perspectives to identify new biological active pep-tides. This study focuses on U9 function, a linear, amphiphilic and polycationic pep-tide isolated from ant Tetramorium bicarinatum venom. It shares physicochemical properties with M-Tb1a, exhibiting cytotoxic effects through membrane permea-bilization. In the present study, we conducted a comparative functional investiga-tion of U9 and M-Tb1a and explored the mechanisms underlying their cytotoxicity against insect cells. After showing that both peptides induced the formation of pores in cell membrane, we demonstrated that U9 induced mitochondrial damage and, at high concentrations, localized into cells and induced caspase activation. This functional investigation highlighted an original mechanism of U9 questioning on potential valorization and endogen activity in T. bicarinatum venom.

Automated summary

This study explores the cytotoxic effects and mechanisms of a peptide called U9 isolated from the venom of Tetramorium bicarinatum, a species of ant. It was found that U9, similar to M-Tb1a, can form pores on the cell membrane, but U9 also induces mitochondrial damage and caspase activation in high concentrations. These findings reveal an original mechanism of cytotoxicity for U9 and raise questions about potential valorization and endogenous activity in T. bicarinatum venom.