Microvesicles Transfer Mitochondria and Increase Mitochondrial Function in Brain Endothelial Cells

Abstract

AbstractWe have demonstrated, for the first time that microvesicles, a sub-type of extracellular vesicles (EVs) derived from hCMEC/D3: a human brain endothelial cell (BEC) line transfer polarized mitochondria to recipient BECs in culture and to neurons in mice acute brain cortical and hippocampal slices. This mitochondrial transfer increased ATP levels by 100 to 200-fold (relative to untreated cells) in the recipient BECs exposed to oxygen-glucose deprivation, an in vitro model of cerebral ischemia. We have also demonstrated that transfer of microvesicles, the larger EV fraction, but not exosomes resulted in increased mitochondrial function in hypoxic endothelial cultures. Gene ontology and pathway enrichment analysis of EVs revealed a very high association to glycolysis-related processes. In comparison to heterotypic macrophage- derived EVs, BEC-derived EVs demonstrated a greater selectivity to transfer mitochondria and increase endothelial cell survival under ischemic conditions.HighlightsMicrovesicles transfer mitochondria to endothelial cells and brain slice neuronsMitochondrial transfer increased ATP in ischemic brain endothelial cells (BECs)Transfer of microvesicles increased mitochondrial function in hypoxic BECsTransfer of exosomes did not affect mitochondrial function in hypoxic BECsHomotypic BEC-derived EVs result in greater ATP levels in the recipient BECs