Mechanism of starvation induced autophagy and apoptosis in the midgut of silkworm, <i>Bombyx mori</i> , based on calcium homeostasis

Starvation can induce autophagy and apoptosis in intestinal cells. To elucidate the underlying mechanisms, we investigated autophagy and apoptosis in the midgut of the model insect, silkworm (Bombyx mori), focusing on calcium homeostasis. The results indicated that the body weight of silkworms decreased, along with damage to the morphology of their digestive tracts and midguts after starvation treatment. Additionally, mitochondrial swelling, autophagy and apoptosis were observable. Further investigation revealed that starvation upregulated the transcription of Ca²⁺ release channel-associated genes (e.g., BmIP3R, BmRyR) but suppressed the expression of Ca²⁺ efflux genes (BmPMCA), resulting in Ca²⁺ overload in midgut cells and subsequent upregulation of BmCalpain transcription. In addition, starvation increased the transcription of key autophagy genes (BmATG5, BmATG7, BmATG8) and the expression of the LC3-II protein. Upon prolonged starvation, the NtATG5 protein levels increased, a process that facilitated the transition from autophagy to apoptosis. These results indicate that Ca²⁺ overload activates the calpain-mediated apoptosis pathway and promotes apoptosis of midgut cells. The present study reveals the significant role that Ca²⁺ plays in the occurrence and transformation of autophagy and apoptosis induced by starvation treatment, thus providing a new research strategy for investigating the damage caused by starvation in biological organisms.