Spatiotemporal control of mitochondrial network dynamics in astroglial cells

Abstract

Mitochondria are increasingly recognized for playing important roles in regulating the evolving metabolic state of mammalian cells. This is particularly true for nerve cells, as dysregulation of mitochondrial dynamics is invariably associated with a number of neuropathies. Accumulating evidence now reveals that changes in mitochondrial dynamics and structure may play equally important roles also in the cell biology of astroglial cells. Astroglial cells display significant heterogeneity in their morphology and specialized functions across different brain regions, however besides fundamental differences they seem to share a surprisingly complex meshwork of mitochondria, which is highly suggestive of tightly regulated mechanisms that contribute to maintain this unique architecture. Here, we summarize recent work performed in astrocytes in situ indicating that this may indeed be the case, with astrocytic mitochondrial networks shown to experience rapid dynamic changes in response to defined external cues. Although the mechanisms underlying this degree of mitochondrial re-shaping are far from being understood, recent data suggest that they may contribute to demarcate astrocyte territories undergoing key signalling and metabolic functions.

Mitochondria-Endoplasmic Reticulum Contacts in Reactive Astrocytes Promote Vascular Remodeling

“…Functionally, this mitochondrial remodeling is also mutually dependent upon a physical tethering with ER membranes (by forming so-called mitochondria-associated membranes, MAMs) where important metabolic functions take place (Scorrano et al, 2019), including lipid trafficking as well as Ca 2+ and reactive oxygen species (ROS) signaling (Csordá s et al, 2018). Intriguingly, evidence exists for complex mitochondrial and ER morphologies in astrocytes in situ, where these organelles have been found to reach fine perisynaptic and endfeet processes (Gö bel et al, 2018;Jackson and Robinson, 2018;Lovatt et al, 2007;Mathiisen et al, 2010;Motori et al, 2013). This spatial distribution suggests the direct contribution of MAMs to specific astrocytic functions, yet whether a dynamic remodeling of these two organelles may effectively couple the acquisition of a reactive state with functional metabolic changes underlying tissue remodeling is unclear.…”

Morphology of Mitochondria in Syncytial Annelid Female Germ-Line Cyst Visualized by Serial Block-Face SEM

“…Analysis of mitochondrial dynamism and the distribution of mitochondrial networks in di erent cell systems have mainly been based on confocal uorescent microscopy [21,[23][24][25][26][27] or high resolution 4Pi microscopy [28,29]. Studies to reveal the complexity of the morphology and distribution of the mitochondria at the ultrastructural level that are not based on single ultrathin sections but in the form of three-dimensional (3D) reconstructions are rare [30].…”

Ca2+ handling at the mitochondria-ER contact sites in neurodegeneration

“…The presence of mitochondria in astrocytes has been documented in soma, branches, and endfeet, while their presence in leaflets is a matter of debates [146,147]. Generally, the size of mitochondria decreases as a function of distance from soma, with exception of endfeet in which relatively large mitochondria are present, often in association with ER [148,149].…”