ATP Metabolism of Astrocytes: Consumption, Regeneration and Restoration

Astrocytes are essential partners of neurons and have many important functions in the brain. Almost all of these astrocytic functions require energy that is provided by cellular adenosine triphosphate (ATP). Accordingly, astrocytes contain a millimolar concentration of cellular ATP that is maintained by continuous and rapid regeneration from adenosine diphosphate (ADP) and adenosine monophosphate (AMP), the main products of cellular energy-consuming reactions. In this article we describe the current knowledge on the cellular content, the consumption and the metabolic regeneration of ATP in astrocytes, explore the consequences of an application of metabolic inhibitors on astrocytic ATP metabolism and summarize the importance of endogenous energy stores and exogenous energy substrates for the maintenance of a high cellular ATP content. In addition, we give insight in recent studies on the visualization of ATP in astrocytes by genetically encoded ATP sensors, summarize the importance of astrocytic ATP release and extracellular ATP processing and discuss recent data on the restoration of ATP in ATP-deprived astrocytes. The current knowledge on the ATP metabolism of astrocytes clearly demonstrates the high potential of this important brain cell type to flexibly use different metabolic pathways and a broad range of endogenous and exogenous sources to maintain, regenerate and restore cellular ATP levels. These processes secure that ATP is continuously available for the many ATP consuming processes that enable astrocytes to perform their functions in the healthy brain.