Regulation of mitochondrial dynamics in astrocytes: Mechanisms, consequences, and unknowns.

Abstract

Astrocytes are the major glial cell in the central nervous system. These polarized cells possess numerous processes that ensheath the vasculature and contact synapses. Astrocytes play important roles in synaptic signaling, neurotransmitter synthesis and recycling, control of nutrient uptake, and control of local blood flow. Many of these processes depend on local metabolism and/or energy utilization. While astrocytes respond to increases in neuronal activity and metabolic demand by upregulating glycolysis and glycogenolysis, astrocytes also possess significant capacity for oxidative (mitochondrial) metabolism. Mitochondria mediate energy supply and metabolism, cellular survival, ionic homeostasis, and proliferation. These organelles are dynamic structures undergoing extensive fission and fusion, directed movement along cytoskeletal tracts, and degradation. While many of the mechanisms underlying the dynamics of these organelles and their physiologic roles have been characterized in neurons and other cells, the roles that mitochondrial dynamics play in glial physiology is less well understood. Recent work from several laboratories has demonstrated that mitochondria are present within the fine processes of astrocytes, that their movement is regulated, and that they contribute to local Ca2+ signaling within the astrocyte. They likely play a role in local ATP production and metabolism, particularly that of glutamate. Here we will review these and other findings describing the mechanism by which mitochondrial dynamics are regulated in astrocytes, how mitochondrial dynamics might influence astrocyte and brain metabolism, and draw parallels to mitochondrial dynamics in neurons. Additionally, we present new analyses of the size, distribution, and dynamics of mitochondria in astrocytes performed using in vivo using 2-photon microscopy.