Transfer of mitochondria from astrocytes to neurons after stroke

Abstract

Recently, it was suggested that neurons can release and transfer damaged mitochondria to astrocytes for disposal and recycling 1. This ability to exchange mitochondria may represent a potential mode of cell-cell signaling in the central nervous system (CNS). Here, we show that astrocytes can also release functional mitochondria that enter into neurons. Astrocytic release of extracellular mitochondria particles was mediated by a calcium-dependent mechanism involving CD38/cyclic ADP ribose signaling. Transient focal cerebral ischemia in mice induced astrocytic mitochondria entry to adjacent neurons that amplified cell survival signals. Suppression of CD38 signaling with siRNA reduced extracellular mitochondria transfer and worsened neurological outcomes. These findings suggest a new mitochondrial mechanism of neuroglial crosstalk that may contribute to endogenous neuroprotective and neurorecovery mechanisms after stroke.