Regulation of neuron-glial signalling by mitochondrial calcium buffering in astrocytes

Josef Kittler (primary)
Neuroscience, Physiology and Pharmacology, Division of Biosciences, Faculty of Life Sciences, UCL
Dimitri Rusakov (secondary)
Queens Square Institute of Neurology, Faculty of Brain Sciences, UCL


Astrocytes maintain brain homeostasis and through the release of glio-transmitters can profoundly modulate neuronal signalling and plasticity (Stephen et al., 2014). Mitochondria are dynamic organelles essential for maintaining cell function, growth, and survival through generation of ATP and buffering intracellular calcium (Devine and Kittler 2018) and their activity-dependent positioning in astrocytes can tune calcium dynamics in astrocyte processes (Stephen et al 2015). Mitochondrial calcium uptake is mediated by the mitochondrial calcium uniporter (MCU) but its role for regulating calcium dynamics in astrocytes and the impact this has on neuronal signalling remains poorly defined, particularly in intact brain tissue.


Devine MJ, Kittler JT. Mitochondria at the neuronal presynapse in health and disease. Nat Rev Neurosci. 2018 Jan 19;19(2):63-80. doi: 10.1038/nrn.2017.170. PubMed PMID: 29348666.

López-Doménech G, Higgs NF, Vaccaro V, Roš H, Arancibia-Cárcamo IL, MacAskill AF, Kittler JT. Loss of Dendritic Complexity Precedes Neurodegeneration in a Mouse Model with Disrupted Mitochondrial Distribution in Mature Dendrites. Cell Rep. 2016 Oct 4;17(2):317-327. doi: 10.1016/j.celrep.2016.09.004. PubMed PMID:27705781;

Mishra A, Reynolds JP, Chen Y, Gourine AV, Rusakov DA, Attwell D. Astrocytes mediate neurovascular signaling to capillary pericytes but not to arterioles. Nat Neurosci. 2016 Dec;19(12):1619-1627. doi: 10.1038/nn.4428.

Savtchenko LP, Bard L, Jensen TP, Reynolds JP, Kraev I, Medvedev N, Stewart MG, Henneberger C, Rusakov DA. Disentangling astroglial physiology with a realistic cell model in silico. Nat Commun. 2018 Sep 3;9(1):3554. doi: 10.1038/s41467-018-05896-w. PubMed PMID: 30177844;

Stephen TL, Gupta-Agarwal S, Kittler JT. Mitochondrial dynamics in astrocytes. Biochem Soc Trans. 2014 Oct;42(5):1302-10. doi: 10.1042/BST20140195. Review.PubMed PMID: 25233407.

Stephen TL, Higgs NF, Sheehan DF, Al Awabdh S, López-Doménech G, Arancibia-Carcamo IL, Kittler JT. Miro1 Regulates Activity-Driven Positioning of Mitochondria within Astrocytic Processes Apposed to Synapses to Regulate Intracellular Calcium Signaling. J Neurosci. 2015 Dec 2;35(48):15996-6011. doi: 10.1523/JNEUROSCI.2068-15.2015. PubMed PMID: 26631479;

Zheng K, Bard L, Reynolds JP, King C, Jensen TP, Gourine AV, Rusakov DA. Time-Resolved Imaging Reveals Heterogeneous Landscapes of Nanomolar Ca(2+) in Neurons and Astroglia. Neuron. 2015 Oct 21;88(2):277-88. doi: 10.1016/j.neuron.2015.09.043. PubMed PMID: 26494277;

Zheng K, Jensen TP, Rusakov DA. Monitoring intracellular nanomolar calcium using fluorescence lifetime imaging. Nat Protoc. 2018 Mar;13(3):581-597. doi: 10.1038/nprot.2017.154. Epub 2018 Feb 22. PubMed PMID: 29470463.

Molecules, cells and industrial biotechnology
Area of Biology
Cell BiologyNeurobiologyPhysiology
Techniques & Approaches
BiochemistryBiophysicsGeneticsImage ProcessingMicroscopy / ElectrophysiologyMolecular BiologySimulation / Modelling