COXIV and SIRT2‐mediated G6PD deacetylation modulate ROS homeostasis to extend pupal lifespan

Low levels of growth hormone 20E in diapause‐destined pupae inhibit both PKA and sirtuin 2 levels, which fail to improve the c‐Myc/TFAM/cytochrome oxidase subunit IV (COXIV) expression and Glucose‐6‐phosphate dehydrogenase (G6PD) activity, and cause increased reactive oxygen species (ROS) levels in mitochondria and cytoplasm to induce diapause and extend the pupal lifespan. However, in nondiapause‐destined pupal brains, the activated PKA‐TFAM‐COXIV pathway and high G6PD activity respond to high 20E levels, which reduce the ROS levels and thus induce pupal‐adult development. Previous studies have shown that high physiological levels of reactive oxygen species (ROS) in the brain promote pupal diapause, which extends the pupal lifespan. However, the molecular mechanisms of ROS generation are unclear. In this paper, we found that mitochondrial ROS (mtROS) levels in the brains of Helicoverpa armigera diapause‐destined pupae (DP) were higher and that the expression of cytochrome oxidase subunit IV (COXIV) was lower than in NP. In addition, downregulating COXIV caused mitochondrial dysfunction which elevated mtROS levels. Protein kinase A (PKA) was downregulated in DP, which led to the downregulated expression of the mitochondrial transcription factor TFAM. Low TFAM activity failed to promote COXIV expression and resulted in the high ROS levels that induced diapause. In addition, low sirtuin 2 expression suppressed glucose‐6‐phosphate dehydrogenase (G6PD) deacetylation at K382, which led to reduced G6PD activity and low NADPH levels, thereby maintaining high levels of ROS. Two proteins, COXIV and G6PD, thus play key roles in the elevated accumulation of ROS that induce diapause and extend the pupal lifespan.