The role of autophagy and lipolysis in survival of astrocytes under nutrient deprivation

Abstract

Astrocytes can survive nutrient deprivation (ND) for days. However, the pro-survival strategy of astrocytes under such a metabolic challenge is still not clear. In the present study, we examined the effects of inhibition of two potential steps in energy acquisition during ND: autophagy (using chloroquine) and lipolysis (using orlistat). The inhibition of autophagy did not show significant effects on cell viability until 8-9 h of ND. From that point onwards, the number of dead cells gradually increased, reaching similar to 60% between 10 and 12 h of ND. In addition, early inhibition of autophagy made astrocytes more vulnerable to the latter ND. The inhibition of lipolysis decreased the viability of cells exposed to ND, but this appeared much later compared to the inhibition of autophagy. The application of orlistat prevented ND-related hyperpolarization of the mitochondrial membrane, and mitochondria became swollen. This study clearly shows that autophagy and lipolysis are essential for the survival of astrocytes under ND conditions, which might be related to their role as neuron-supporting cells.