Editors' ChoiceNeuroscience

Astrocytes donate mitochondria

Sci. Signal.  02 Aug 2016:
Vol. 9, Issue 439, pp. ec174
DOI: 10.1126/scisignal.aah6674

Astrocytes are glial cells that perform many functions in the central nervous system, such as providing trophic support for neurons and promoting repair. Astrocytes also help protect neurons from oxidative stress and can take up and degrade damaged mitochondria released from neurons. Hayakawa et al. found that cultured rat cortical astrocytes released fragments of mitochondria into the culture medium, and these fragments were taken up by cultured rat cortical neurons. Depriving cultured neurons of oxygen and glucose reduced both the intracellular adenosine 5′-triphosphate (ATP) concentration and cell viability. Adding astrocyte-conditioned culture medium to oxygen- and glucose-deprived neurons restored ATP accumulation and improved survival but not if the medium had been depleted of mitochondrial fragments or treated with a pharmacological inhibitor of the mitochondrial citric acid cycle. These effects required CD38 in astrocytes. CD38 is an enzyme in mitochondria that synthesizes the calcium-mobilizing second messenger cyclic ADP-ribose (cADPR), and stimulating astrocytes with cADPR increased mitochondrial release. When astrocyte-derived mitochondrial fragments were injected into the cerebral cortex of mice following transient focal cerebral ischemia to mimic stroke, the mitochondrial fragments were taken up by neurons. Similarly, subjecting transgenic mice with fluorescently labeled astrocytes to cerebral ischemia induced the appearance of fluorescently labeled mitochondria in neurons around the site of ischemic damage. These neurons exhibited increased abundance of a mitochondrial marker and increased activation of cell survival factors. CD38 abundance increased in the cortex of mice subjected to focal cerebral ischemia, and silencing CD38 by RNA interference decreased the number of mitochondria in neurons, reduced the abundance of a marker of neurite outgrowth, and exacerbated neurological symptoms following stroke. How astrocyte-released mitochondria enter neurons was not determined, but these findings demonstrate that astrocytes can support neurons by releasing mitochondria that help the neurons recover from ischemia.

K. Hayakawa, E. Esposito, X. Wang, Y. Terasaki, Y. Liu, C. Xing, X. Ji, E. H. Lo, Transfer of mitochondria from astrocytes to neurons after stroke. Nature 535, 551–555 (2016). [PubMed]

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