Reweaving the Fabric of Mitochondrial Contact Sites in Astrocytes

Matteo Bergami,Elisa Motori

doi:10.3389/fcell.2020.592651

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.

Highlights

Substantial effort is being made in understanding the mechanisms that regulate tethering between mitochondria and other organelles, the endoplasmic reticulum (ER), given that important functions have been ascribed to these mitochondria-ER contacts (MERCs) (Csordas et al, 2018)
While the precise mechanisms underlying this non-cell-autonomous effect on endothelial cells can only be speculated, these findings suggest that a dynamic reorganization of MERCs at precise locations of the astrocyte may serve to generate local metabolic domains important for tissue healing
Recent progress in microscopy and genetic techniques began unveiling an important role played by mitochondria and ER networks in regulating astrocytic functions, yet our understanding of organelle physiology and “contact-ology” in astrocytes is still rudimentary

Summary

Introduction

Substantial effort is being made in understanding the mechanisms that regulate tethering between mitochondria and other organelles, the endoplasmic reticulum (ER), given that important functions have been ascribed to these mitochondria-ER contacts (MERCs) (Csordas et al, 2018). Alongside with their elaborated morphologies, these two organelles were found to be differentially distributed across cellular territories (Mathiisen et al, 2010; Cali et al, 2019; Göbel et al, 2020) and to give rise to a significant extent of MERCs in remote regions of the astrocyte – like the perivascular endfeet – where their specialized functions are most likely sustaining important roles in physiological and disease settings.

Results

Conclusion