Research Paper Volume 10, Issue 5 pp 1053—1072
Deacetylation of metabolic enzymes by Sirt2 modulates pyruvate homeostasis to extend insect lifespan
- 1 State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, China
received: February 10, 2018 ; accepted: May 8, 2018 ; published: May 16, 2018 ;https://doi.org/10.18632/aging.101447
How to Cite
Copyright: Wang et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Diapause in insects is akin to dauer in Caenorhabditis elegans and hibernation in vertebrates. Diapause causes a profound extension of lifespan by low metabolic activity. However, the detailed regulatory mechanisms for low metabolic activity remain unknown. Here, we showed that low pyruvate levels are present in the brains of diapause-destined pupae of the cotton bollworm Helicoverpa armigera, and three enzymes pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), and phosphoglycerate mutase (PGAM) are closely correlated with pyruvate homeostasis. Notably, Sirt2 can deacetylate the three enzymes to increase their activity in vitro. Thus, low Sirt2 expression in the brains of diapause individuals decreases PK and PEPCK protein levels as well as PGAM activity, resulting in low pyruvate levels and low tricarboxylic acid cycle activity and eventually inducing diapause initiation by low metabolic activity. These findings suggest that pyruvate is a checkpoint for development or lifespan extension, and Sirt2 is a negative regulator to extend lifespan in insects.