Mitochondrial Extracellular Vesicles - Origins and Roles

Abstract

Extracellular vesicles (EVs) have emerged in the last decade as critical cell-to-cell communication devices used to carry nucleic acids and proteins between cells. EV cargo includes plasma membrane and endosomal proteins, but EVs also contain material from other cellular compartments, including mitochondria. Within cells, mitochondria are responsible for a large range of metabolic reactions, but they can also produce damaging levels of reactive oxygen species and induce inflammation when damaged. Consistent with this, recent evidence suggests that EV-mediated transfer of mitochondrial content alters metabolic and inflammatory responses of recipient cells. As EV mitochondrial content is also altered in some pathologies, this could have important implications for their diagnosis and treatment. In this review, we will discuss the nature and roles of mitochondrial EVs, with a special emphasis on the nervous system.

Keywords: extracellular vesicle; inflammation; metabolism; mitochondria; mitochondrial quality control.

FIGURE 1

Model for the roles and mechanisms of secretion of mitochondrial EVs. Under basal conditions, MDVs are required to package mitochondrial components into mitochondrial EVs, which serve to increase OXPHOS in recipient cells. In this setting, oxidized mitochondrial components are not released into EVs but rather sent to lysosomes for degradation through a different type of MDV (Parkin-dependent). On the other hand, pro-inflammatory stimuli like LPS cause the release of free mitochondria or mitochondria packaged within microvesicles that further stimulate inflammation.