微泡
线粒体
细胞外小泡
生物
细胞生物学
人口
细胞外
遗传学
小RNA
医学
基因
环境卫生
作者
Pasquale D’Acunzo,Rocío Pérez‐González,Yohan Kim,Tal Hargash,Chelsea Miller,Melissa J. Alldred,Hediye Erdjument‐Bromage,Sai C. Penikalapati,Monika Pawlik,Mitsuo Shimada,Mariko Saito,Stephen D. Ginsberg,Thomas A. Neubert,Chris N. Goulbourne,Efrat Levy
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2021-02-12
卷期号:7 (7)
被引量:129
标识
DOI:10.1126/sciadv.abe5085
摘要
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 mitochondrial 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 mitochondrial constituents and that their levels and cargo are altered during pathophysiological processes where mitochondrial 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.
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