Spatiotemporal control of mitochondrial network dynamics in astroglial cells

https://doi.org/10.1016/j.bbrc.2017.06.191Get rights and content

Highlights

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    Astrocytes display highly complex mitochondrial architectures in vivo.

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    Mitochondrial trafficking and dynamics in astrocytes are regulated.

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    Mitochondria critically contribute to astrocyte Ca2+ handling.

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    Astrocyte reacting to injury undergo marked changes in mitochondrial dynamics.

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.

Section snippets

Unique architecture of the astrocytic mitochondrial network

Owing to a very complex tridimensional morphology, which in most astrocytes is characterized by a number of major processes giving rise to thousands of ramified branchlets and leaflets, a detailed analysis of the mitochondrial network architecture in these cells in situ has been elusive. Only during the last decade electron microscopy studies have started to ascertain that astrocytes, and astroglial cells in general, are surprisingly enriched in mitochondria [12], [19], [20], [21]. These

Mitochondrial trafficking and dynamics in astrocytes in situ are regulated

The complex and seemingly heterogeneous structure of the mitochondrial network in astrocytes is highly suggestive of prominent ongoing trafficking and dynamics of mitochondria. In mammals, experiments conducted predominately in neurons revealed that specific adaptor proteins (e.g., Miro and TRAKs) sit right at the core of the mitochondrial trafficking machinery, and mediate the reversible binding of mitochondria to proper motor proteins (kinesin and dynein) [28]. While the exact stoichiometry

Mutual regulation of mitochondrial and Ca2+ dynamics in astrocytes

On account of their highly ramified morphology as well as expression of a wide repertoire of membrane receptors, transporters and channels, astrocytes are thought of regulating locally tissue homeostasis, including ions concentration and neuro/glio-transmitter uptake and release [3]. At the core of this capability of sensing and signaling regionalized changes in the activity of, e.g., nearby synapses is a very unique spatiotemporal regulation of Ca2+ events [46], [47]. In fact, unlike neurons,

Mitochondrial dynamics and quality control in astrocytes reacting to injury

Over the course of the last years, astrocytes have gradually but progressively emerged as a group of cells invariably involved in virtually most brain diseases. While current evidence indicates that astrocytes do exert various and important functions in the healthy brain, presumably owning to their increasingly recognized cellular heterogeneity [27], to date we still know surprisingly little about the sub-cellular changes these cells experience when facing challenging and harmful conditions.

Conclusions

Despite growing evidence for an important role of astrocytes in modulating synaptic and vascular functions, still little is known about how these cells may efficiently couple their response to external stimuli with local intracellular changes in their signalling and metabolic states. Our knowledge about the molecular processes underlying these changes is still rudimentary, yet recent progress in imaging techniques and genetic tools began to unveil a previously unappreciated complexity in the

Funding

This work was supported by the UoC advanced post-doc grant program, Deutsche Forschungsgemeinschaft (CRC 1218) and European Research Council (ERC-StG-2015, grant number 67844) to M.B.

Conflict of interest

No potential conflicts of interest were disclosed.

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