The unfolded protein response modulates the autophagy-mediated egg production in the mosquito Aedes aegypti

Mosquitoes must feed on vertebrate blood for egg development. As a consequence, some mosquito species are vectors for pathogens that cause devastating diseases in humans. Hence, understanding the mechanisms that control egg developmental cycles is important for developing novel approaches for the control of mosquito-borne diseases. The unfolded protein response (UPR) is a cellular stress response related to endoplasmic reticulum (ER) stress. The UPR is activated in response to an accumulation of unfolded or misfolded proteins in the ER. Massive proteins have been shown to be produced during egg development, and it is obvious that unfolded or misfolded proteins may arise during vitellogenesis. It has been shown that autophagy in the mosquito fat body plays a central role in the progression of gonadotrophic cycles in the mosquito Aedes aegypti. However, the molecular mechanisms underlying the induction of UPR and the correlation between UPR and autophagy remain unclear. Here, we demonstrate that autophagy is activated during vitellogenesis and that the activation of autophagy is correlated with the UPR. We also show that the expressions of UPR and autophagy can be induced in an in vitro fat body culture system through an amino acid treatment. In addition, the expressions of UPR, autophagy-specific markers and vitellogenin were also induced during dithiothreitol treatment. Interestingly, the silencing of UPR-related genes significantly reduced the expression of autophagy-specific markers and inhibited mosquito fecundity. Taken together, we conclude that autophagy-mediated egg production in the mosquito A. aegypti is regulated by UPR.