Hexokinase is a key regulator of energy metabolism and ROS activity in insect lifespan extension

• Published in: Aging (Albany, NY.) Vol. 8; no. 2; pp. 245 - 259
• Main Authors: Lin, Xian-Wu, Xu, Wei-Hua
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 01.02.2016
• Subjects: Animals; Blotting, Western; Chromatin Immunoprecipitation; Diapause, Insect - physiology; Electrophoretic Mobility Shift Assay; Energy Metabolism - physiology; Gene Knockdown Techniques; Hexokinase - metabolism; Insect Proteins - physiology; Longevity - physiology; Moths - physiology; Pupa; Real-Time Polymerase Chain Reaction; Research Paper; transcription factor; Helicoverpa armigera; developmental arrest; gene regulation; hexokinase
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.100885

Developmental arrest (diapause) is a 'non-aging' state that is similar to the Caenorhabditis elegans dauer stage and Drosophila lifespan extension. Diapause results in low metabolic activity and a profound extension of insect lifespan. Here, we cloned the Helicoverpa armigera Hexokinase (HK) gene, a gene that is critical for the developmental arrest of this species. HK expression and activity levels were significantly increased in nondiapause-destined pupae compared with those of diapause-destined pupae. Downregulation of HK activity reduced cell viability and delayed pupal development by reducing metabolic activity and increasing ROS activity, which suggests that HK is a key regulator of insect development. We then identified the transcription factors Har-CREB, -c-Myc, and -POU as specifically binding the Har-HK promoter and regulating its activity. Intriguingly, Har-POU and -c-Myc are specific transcription factors for HK expression, whereas Har-CREB is nonspecific. Furthermore, Har-POU and -c-Myc could respond to ecdysone, which is an upstream hormone. Therefore, low ecdysone levels in diapause-destined individuals lead to low Har-POU and -c-Myc expression levels, ultimately repressing Har-HK expression and inducing entry into diapause or lifespan extension.