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

被引：190

作者：

D'Acunzo, Pasquale ^{[1
,2
]}

Perez-Gonzalez, Rocio ^{[1
,2
,10
]}

Kim, Yohan ^{[1
,2
]}

Hargash, Tal ^{[1
]}

Miller, Chelsea ^{[1
]}

Alldred, Melissa J. ^{[1
,2
]}

Erdjument-Bromage, Hediye ^{[3
,4
]}

Penikalapati, Sai C. ^{[1
]}

Pawlik, Monika ^{[1
]}

Saito, Mitsuo ^{[2
,5
]}

Saito, Mariko ^{[2
,6
]}

Ginsberg, Stephen D. ^{[1
,2
,7
,8
]}

Neubert, Thomas A. ^{[3
,4
]}

Goulbourne, Chris N. ^{[1
]}

Levy, Efrat ^{[1
,2
,7
,9
]}

机构：

[1] Nathan S Kline Inst Psychiat Res, Ctr Dementia Res, Orangeburg, NY 10962 USA

[2] NYU, Dept Psychiat, Sch Med, New York, NY 10016 USA

[3] NYU, Dept Cell Biol, Sch Med, New York, NY 10016 USA

[4] NYU, Kimmel Ctr Biol & Med, Skirball Inst, Sch Med, New York, NY 10016 USA

[5] Nathan S Kline Inst Psychiat Res, Div Analyt Psychopharmacol, Orangeburg, NY 10962 USA

[6] Nathan S Kline Inst Psychiat Res, Div Neurochem, Orangeburg, NY 10962 USA

[7] NYU, Neurosci Inst, Sch Med, New York, NY 10016 USA

[8] NYU, Dept Neurosci & Physiol, Sch Med, New York, NY 10016 USA

[9] NYU, Dept Biochem & Mol Pharmacol, Sch Med, New York, NY 10016 USA

[10] Hosp Santa Creu & Sant Pau, Dept Neurol, Ctr Networked Biomed Res Neurodegenerat Dis CIBER, Barcelona, Spain

来源：

SCIENCE ADVANCES | 2021年 / 7卷 / 07期

关键词：

AMYLOID PRECURSOR PROTEIN; CA1 PYRAMIDAL NEURONS; MICROARRAY ANALYSIS; MOUSE MODEL; MITOPHAGY; DYSFUNCTION; BRAIN; PATHWAY; INDUCTION; MEMBRANE;

D O I：

10.1126/sciadv.abe5085

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

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 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.

引用

页数：18

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