Research Article: Deacetylation of metabolic enzymes by Sirt2 modulates pyruvate homeostasis to extend insect lifespan

Date Published: May 16, 2018

Publisher: Impact Journals

Author(s): Tao Wang, Shao-Lei Geng, Yu-Min Guan, Wei-Hua Xu.


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.

Partial Text

Most insect species have evolved a special stage of developmental arrest (diapause) in response to adverse environmental conditions [1]. Diapause, a specific entomological term, is used to describe the slow development as dauer in Caenorhabditis elegans [2] and hibernation in vertebrates [3] with low metabolic activity. For example, the cotton bollworm Helicoverpa armigera larvae are reared during periods of short day length and low temperatures (20 °C), and the pupae enter diapause with low metabolic activity [4]. Compared to their nondiapause counterparts, reared during periods of long day length under the same temperatures, the lifespan of diapause pupa is more than 3 times longer [4]. Therefore, this species is an excellent model for lifespan research [4].

Insect brain is a center for regulating diapause, and down regulation of brain activity in diapause-destined individuals leads to a decreased activity in other tissues or organs to cause diapause initiation [33]. Therefore, metabolic depression is a universal character of diapause among many species [34–36], and the most important function of sugar metabolism is related to energy production. Pyruvate is derived from glycolysis and subsequently converted into acetyl-coenzyme A to feed the TCA cycle. In the present study, low levels of pyruvate induce diapause initiation, whereas high levels of pyruvate promote pupal-adult development, indicating that pyruvate is a key regulator in development or diapause.




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