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Reweaving the Fabric of Mitochondrial Contact Sites in Astrocytes - PubMed

  • ️Wed Jan 01 2020

Reweaving the Fabric of Mitochondrial Contact Sites in Astrocytes

Matteo Bergami et al. Front Cell Dev Biol. 2020.

Abstract

The endoplasmic reticulum (ER) and mitochondria are classically regarded as very dynamic organelles in cell lines. Their frequent morphological changes and repositioning underlie the transient generation of physical contact sites (so-called mitochondria-ER contacts, or MERCs) which are believed to support metabolic processes central for cellular signaling and function. The extent of regulation over these organelle dynamics has likely further achieved a higher level of complexity in polarized cells like neurons and astrocytes to match their elaborated geometries and specialized functions, thus ensuring the maintenance of MERCs at metabolically demanding locations far from the soma. Yet, live imaging of adult brain tissue has recently revealed that the true extent of mitochondrial dynamics in astrocytes is significantly lower than in cell culture settings. On one hand, this suggests that organelle dynamics in mature astroglia in vivo may be highly regulated and perhaps triggered only by defined physiological stimuli. On the other hand, this extent of control may greatly facilitate the stabilization of those MERCs required to maintain regionalized metabolic domains underlying key astrocytic functions. In this perspective, we review recent evidence suggesting that the resulting spatial distribution of mitochondria and ER in astrocytes in vivo may create the conditions for maintaining extensive MERCs within specialized territories - like perivascular endfeet - and discuss the possibility that their enrichment at these distal locations may facilitate specific forms of cellular plasticity relevant for physiology and disease.

Keywords: MERCs; Mfn2; astrocytes; calcium; endfoot; endoplasmic reticulum; mitochondria; mitochondrial dynamics.

Copyright © 2020 Bergami and Motori.

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Figures

FIGURE 1
FIGURE 1

Overview of astrocyte functions in the neurovascular unit. Scheme illustrating the main metabolic functions of astrocytes at their perivascular (endfeet) and perisynaptic processes. Glucose is mostly taken up via the endfeet, where also ions and water molecules can be actively exchanged with the blood-brain barrier. Following glycolytic conversion to pyruvate, glucose can be utilized as energy substrate by astrocytic mitochondria or further converted into lactate to fuel synaptic transmission. At perisynaptic processes, astrocytes contribute to replenish the glutamate pool of neurotransmitters via the glutamate-glutamine cycle. Dashed lines between metabolites indicate a metabolic conversion. Plasma membrane transporters and ionic pumps are indicated with blue (for astrocytes) or gray (for neurons) symbols.

FIGURE 2
FIGURE 2

Asymmetric distribution of MERCs in astrocytic processes. (A) Example of a cortical astrocyte co-transduced with ER-GFP and mito-RFP viruses, showing the distribution of both organelles in vivo across astrocytic territories, particularly perivascular endfeet and fine branchlets. Immunostaining against the endothelial marker CD31, labeling the vasculature, is shown. (B) Scheme of an astrocyte showing the location of somas, main branches, perisynaptic, and perivascular processes (the latter ones visible as tube-like structures). (C) Electron microscopic pictures of distinct portions of the astrocyte (dashed areas correspond to astrocytic processes). While in main branches and endfeet large mitochondria are often visible, in processes surrounding synapses mitochondria display a smaller size. In each panel, mitochondria and ER are highlighted in different colors (yellow, mitochondria; red, ER). Lower panels depict zooms of the boxed areas, pointing to putative MERCs. EC, endothelial cell.

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