Mitovesicles are a novel population of extracellular vesicles of mitochondrial origin altered in Down syndrome

Mitochondrial dysfunction is an established hallmark of aging and neurodegenerative disorders such as Down syndrome (DS) and Alzheimer's disease (AD). Using a high-resolution density gradient separation of extracellular vesicles (EVs) isolated from murine and human DS and diploid control brains, we identify and characterize a previously unknown population of double-membraned EVs containing multiple mitochondria! proteins distinct from previously described EV subtypes, including microvesicles and exosomes. We term these newly identified mitochondria-derived EVs mitovesicles. We demonstrate that brain-derived mitovesicles contain a specific subset of mitochondria! constituents and that their levels and cargo are altered during pathophysiological processes where mitochondria! dysfunction occurs, including in DS. The development of a method for the selective isolation of mitovesicles paves the way for the characterization in vivo of biological processes connecting EV biology and mitochondria dynamics and for innovative therapeutic and diagnostic strategies.

Automated summary

The study identified a previously unknown population of double-membraned EVs called mitovesicles, which contain specific mitochondrial constituents and undergo changes during pathophysiological processes involving mitochondrial dysfunction. The development of a method for the selective isolation of mitovesicles opens up new possibilities for characterizing biological processes connecting EV biology and mitochondria dynamics in vivo, as well as for innovative therapeutic and diagnostic strategies.