Notch regulates mitochondrial activity in pupal diapause of Helicoverpa armigera through the c-Myc-TFAM pathway.

Insects enter diapause in order to avoid adverse environmental conditions. Diapause is a complex physiological process regulated by multiple signaling pathways, and the molecular regulatory mechanisms remain incompletely understood. Notch signaling pathway is evolutionarily conserved and plays diverse roles in insect development, including cell fate determination, organ growth, and tissue patterning. Recent research has demonstrated that Notch signaling is indispensable for both the maintenance and recovery of dauer (a diapause-like state in Caenorhabditis elegans), however, the role of Notch signaling in insect diapause has not been previously documented. In the current study, we therefore investigated the expression pattern of Notch in diapausing and developing pupae of Helicoverpa armigera, aiming to elucidate its potential regulatory mechanism of Notch in pupal diapause. We found that the protein expression of intracellular domain of Notch (NICD, the functional part of Notch) was lower in diapause-destined pupae than that in non-diapause pupae. Inhibiting the NICD expression by LY411575 delayed the development of non-diapause pupae. Furthermore, NICD knockdown (via dsRNA) or pharmacological inhibition downregulated the mitochondrial DNA (mtDNA) levels and mitochondrial activity by regulating the transcription factors c-Myc and TFAM. Consistent with previous findings that diapausing brains have lower mitochondrial activity, we propose that Har-NICD might participate in diapause regulation by modulating mitochondrial activity via the c-Myc-TFAM axis.