Therapeutic use of extracellular mitochondria in CNS injury and disease

In the central nervous system (CNS), neuronal functionality is highly dependent on mitochondrial integrity and activity. In the context of a damaged or diseased brain, mitochondrial dysfunction leads to reductions in ATP levels, thus impairing ATP-dependent neural firing and neurotransmitter dynamics. Restoring mitochondrial ability to generate ATP may be a basic premise to restore neuronal functionality. Recently, emerging data in rodent and human studies suggest that mitochondria and its components are surprisingly released into extracellular space and potentially transferred between cells. Transferred mitochondria may support oxidative phosphorylation in recipient cells. In this mini-review, we (a) survey recent findings in cell to cell mitochondrial transfer and the presence of cell-free extracellular mitochondria and its components, (b) review experimental details of how to detect extracellular mitochondria and mitochondrial transfer in the CNS, (c) discuss strategies and tissue sources for mitochondria isolation, and (d) explore exogenous mitochondrial transplantation as a novel approach for CNS therapies.