Mitochondria and Lysosomes Participate in Vip3Aa-Induced Spodoptera frugiperda Sf9 Cell Apoptosis

Abstract

Vip3Aa, a soluble protein produced by certain Bacillus thuringiensis strains, is capable of inducing apoptosis in Sf9 cells. However, the apoptosis mechanism triggered by Vip3Aa is unclear. In this study, we found that Vip3Aa induces mitochondrial dysfunction, as evidenced by signs of collapse of mitochondrial membrane potential, accumulation of reactive oxygen species, release of cytochrome c, and caspase-9 and -3 activation. Meanwhile, our results indicated that Vip3Aa reduces the ability of lysosomes in Sf9 cells to retain acridine orange. Moreover, pretreatment with Z-Phe-Tyr-CHO (a cathepsin L inhibitor) or pepstatin (a cathepsin D inhibitor) increased Sf9 cell viability, reduced cytochrome c release, and decreased caspase-9 and -3 activity. In conclusion, our findings suggested that Vip3Aa promotes Sf9 cell apoptosis by mitochondrial dysfunction, and lysosomes also play a vital role in the action of Vip3Aa.

Current Insights on Vegetative Insecticidal Proteins (Vip) as Next Generation Pest Killers

“…Another study has evidenced the involvement of regulatory proteins and lysosomes in apoptosis. Furthermore, symptoms of apoptosis and mitochondrial collapse are prevalent in sf9 cells when administered Vip3Aa, such as the accumulation of reactive oxygen species (ROS), caspases (caspase 3,9), and cytochrome c [66] ( Figure 3). Because of the lack of sound information, more investigation is needed to clarify the downstream mechanism of Vip3 induced apoptosis and cell death.…”

Vegetative Insecticidal Protein (Vip): A Potential Contender From Bacillus thuringiensis for Efficient Management of Various Detrimental Agricultural Pests

“…Recently, efforts have been made to dissect the mitochondrial-mediated pathway of apoptotic cell death, which has revealed the importance of lysosomes in this process ( Hou et al, 2020 ). The toxin induces the build-up of reactive oxygen species, cytochrome release, disruption of mitochondrial membrane potential, and activation of caspases (3 and 9) resulting in morphological changes (swelling and distorted cristae); overall dysfunctioning of mitochondria and finally reduced the viability of Sf9 cells.…”

Structural and Functional Insights into the C-terminal Fragment of Insecticidal Vip3A Toxin of Bacillus thuringiensis

“…Since their discovery in 1996 [24], Vip3A proteins have been the subject of intensive research. It has been reported that Vip3A stimulates membrane pore formation and apoptosis upon binding to target cells, which is proposed to be responsible for its cytotoxic effects [12,[25][26][27]. The scavenger receptor class C like protein (Sf-SR-C) and the fibroblast growth factor receptor (Fgfr) have been reported as potential receptors for Vip3A [10,11].…”