Mitovesicles are a novel population of extracellular vesicles of mitochondrial origin altered in down syndrome
D'Acunzo, Pasquale (New York University. School of Medicine. Department of Psychiatry)
Pérez-González, Rocío (Institut d'Investigació Biomèdica Sant Pau)
Kim, Yohan (New York University. School of Medicine. Department of Psychiatry)
Hargash, Tal (Center for Dementia Research. Nathan S. Kline Institute for Psychiatric Research)
Miller, Chelsea (Center for Dementia Research. Nathan S. Kline Institute for Psychiatric Research)
Alldred, Melissa J. (Department of Psychiatry. New York University. School of Medicine)
Erdjument-Bromage, Hediye (New York University. School of Medicine. Kimmel Center for Biology and Medicine. The Skirball Institute)
Penikalapati, Sai Charan (Center for Dementia Research. Nathan S. Kline Institute for Psychiatric Research)
Pawlik, Monika (Center for Dementia Research. Nathan S. Kline Institute for Psychiatric Research)
Saito, Mitsuo (Division of Neurochemistry. Nathan S. Kline Institute for Psychiatric Research)
Saito, Mariko (New York University School of Medicine. Department of Psychiatry)
Ginsberg, Stephen D. (New York University. School of Medicine. Department of Neuroscience and Physiology)
Neubert, Thomas A. (Kimmel Center for Biology and Medicine. The Skirball Institute. New York University. School of Medicine)
Goulbourne, Chris N. (Center for Dementia Research. Nathan S. Kline Institute for Psychiatric Research)
Levy, Efrat (Department of Biochemistry and Molecular Pharmacology. New York University. School of Medicine)

Fecha:	2021
Resumen:	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.
Nota:	Altres ajuts: National Institute on Aging (AG017617, AG056732, and AG057517); National Institute on Drug Abuse (DA044489); NIH Instrumentation Grant (S10RR027990).
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Alzheimer's disease ; Biological process ; Density gradient separation ; Diagnostic strategy ; Mitochondrial dysfunction ; Mitochondrial protein ; Neurodegenerative disorders ; Selective isolation ; Alzheimer Disease ; Animals ; Down Syndrome ; Exosomes ; Extracellular Vesicles ; Humans ; Mice
Publicado en:	Science advances, Vol. 7 Núm. 7 (december 2021) , p. eabe5085, ISSN 2375-2548

DOI: 10.1126/sciadv.abe5085
PMID: 33579698

19 p, 6.0 MB

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