AKT mediated glycolytic shift regulates autophagy in classically activated macrophages.

AKT mediated glycolytic shift regulates autophagy in classically activated macrophages.
Int J Biochem Cell Biol. 2015 Jul 26;
Authors: Matta SK, Kumar D
Abstract
Autophagy is considered as an innate defense mechanism primarily due to its role in the targeting of intracellular pathogens for lysosomal degradation. Here we report inhibition of autophagy as an adaptive response in classically activated macrophages that helps achieve high cellular ROS production and cell death-another hallmark of innate mechanisms. We show prolonged classical activation of Raw 264.7 macrophages by treating them with IFN-γ and LPS inhibited autophagy. The inhibition of autophagy was dependent on nitric oxide (NO) production which activated the AKT-mTOR signaling, the known negative regulators of autophagy. Autophagy inhibition in these cells was accompanied with a shift to aerobic glycolysis along with a decline in the mitochondrial membrane potential (MOMP). The decline in MOMP coupled with autophagy inhibition led to increased mitochondrial content and considerably elevated cellular ROS, eventually causing cell death. Next, using specific siRNA mediated knockdowns we show AKT was responsible for the glycolytic shift and autophagy inhibition in activated macrophages. Surprisingly, AKT knockdown in activated macrophages also rescued them from cell death. Finally we show that AKT mediated autophagy inhibition in the activated macrophages correlated with th...

Source: The International Journal of Biochemistry and Cell Biology - July 26, 2015 Category: Biochemistry Authors: Matta SK, Kumar D Tags: Int J Biochem Cell Biol Source Type: research