Cocaine perturbs mitovesicle biology in the brain

Abstract Cocaine, an addictive psychostimulant, has a broad mechanism of action, including the induction of a wide range of alterations in brain metabolism and mitochondrial homeostasis. Our group recently identified a subpopulation of non‐microvesicular, non‐exosomal extracellular vesicles of mitoc...

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Main Authors: Pasquale D'Acunzo, Jonathan M. Ungania, Yohan Kim, Bryana R. Barreto, Steven DeRosa, Monika Pawlik, Stefanie Canals‐Baker, Hediye Erdjument‐Bromage, Audrey Hashim, Chris N. Goulbourne, Thomas A. Neubert, Mariko Saito, Henry Sershen, Efrat Levy
Format: Article
Language:English
Published: Wiley 2023-01-01
Series:Journal of Extracellular Vesicles
Subjects:
Online Access:https://doi.org/10.1002/jev2.12301
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author Pasquale D'Acunzo
Jonathan M. Ungania
Yohan Kim
Bryana R. Barreto
Steven DeRosa
Monika Pawlik
Stefanie Canals‐Baker
Hediye Erdjument‐Bromage
Audrey Hashim
Chris N. Goulbourne
Thomas A. Neubert
Mariko Saito
Henry Sershen
Efrat Levy
author_facet Pasquale D'Acunzo
Jonathan M. Ungania
Yohan Kim
Bryana R. Barreto
Steven DeRosa
Monika Pawlik
Stefanie Canals‐Baker
Hediye Erdjument‐Bromage
Audrey Hashim
Chris N. Goulbourne
Thomas A. Neubert
Mariko Saito
Henry Sershen
Efrat Levy
author_sort Pasquale D'Acunzo
collection DOAJ
description Abstract Cocaine, an addictive psychostimulant, has a broad mechanism of action, including the induction of a wide range of alterations in brain metabolism and mitochondrial homeostasis. Our group recently identified a subpopulation of non‐microvesicular, non‐exosomal extracellular vesicles of mitochondrial origin (mitovesicles) and developed a method to isolate mitovesicles from brain parenchyma. We hypothesised that the generation and secretion of mitovesicles is affected by mitochondrial abnormalities induced by chronic cocaine exposure. Mitovesicles from the brain extracellular space of cocaine‐administered mice were enlarged and more numerous when compared to controls, supporting a model in which mitovesicle biogenesis is enhanced in the presence of mitochondrial alterations. This interrelationship was confirmed in vitro. Moreover, cocaine affected mitovesicle protein composition, causing a functional alteration in mitovesicle ATP production capacity. These data suggest that mitovesicles are previously unidentified players in the biology of cocaine addiction and that target therapies to fine‐tune brain mitovesicle functionality may be beneficial to mitigate the effects of chronic cocaine exposure.
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spelling doaj.art-ef1beae90ae14629ba8533a2a1dcee1e2023-01-24T09:48:29ZengWileyJournal of Extracellular Vesicles2001-30782023-01-01121n/an/a10.1002/jev2.12301Cocaine perturbs mitovesicle biology in the brainPasquale D'Acunzo0Jonathan M. Ungania1Yohan Kim2Bryana R. Barreto3Steven DeRosa4Monika Pawlik5Stefanie Canals‐Baker6Hediye Erdjument‐Bromage7Audrey Hashim8Chris N. Goulbourne9Thomas A. Neubert10Mariko Saito11Henry Sershen12Efrat Levy13Center for Dementia Research Nathan S. Kline Institute for Psychiatric Research Orangeburg New York USACenter for Dementia Research Nathan S. Kline Institute for Psychiatric Research Orangeburg New York USACenter for Dementia Research Nathan S. Kline Institute for Psychiatric Research Orangeburg New York USACenter for Dementia Research Nathan S. Kline Institute for Psychiatric Research Orangeburg New York USACenter for Dementia Research Nathan S. Kline Institute for Psychiatric Research Orangeburg New York USACenter for Dementia Research Nathan S. Kline Institute for Psychiatric Research Orangeburg New York USADivision of Neurochemistry Nathan S. Kline Institute for Psychiatric Research Orangeburg New York USADepartment of Cell Biology New York University Grossman School of Medicine New York New York USADivision of Neurochemistry Nathan S. Kline Institute for Psychiatric Research Orangeburg New York USACenter for Dementia Research Nathan S. Kline Institute for Psychiatric Research Orangeburg New York USADepartment of Cell Biology New York University Grossman School of Medicine New York New York USADepartment of Psychiatry New York University Grossman School of Medicine New York New York USADepartment of Psychiatry New York University Grossman School of Medicine New York New York USACenter for Dementia Research Nathan S. Kline Institute for Psychiatric Research Orangeburg New York USAAbstract Cocaine, an addictive psychostimulant, has a broad mechanism of action, including the induction of a wide range of alterations in brain metabolism and mitochondrial homeostasis. Our group recently identified a subpopulation of non‐microvesicular, non‐exosomal extracellular vesicles of mitochondrial origin (mitovesicles) and developed a method to isolate mitovesicles from brain parenchyma. We hypothesised that the generation and secretion of mitovesicles is affected by mitochondrial abnormalities induced by chronic cocaine exposure. Mitovesicles from the brain extracellular space of cocaine‐administered mice were enlarged and more numerous when compared to controls, supporting a model in which mitovesicle biogenesis is enhanced in the presence of mitochondrial alterations. This interrelationship was confirmed in vitro. Moreover, cocaine affected mitovesicle protein composition, causing a functional alteration in mitovesicle ATP production capacity. These data suggest that mitovesicles are previously unidentified players in the biology of cocaine addiction and that target therapies to fine‐tune brain mitovesicle functionality may be beneficial to mitigate the effects of chronic cocaine exposure.https://doi.org/10.1002/jev2.12301cocaineexosomeextracellular vesiclemicrovesiclemitochondriamitophagy
spellingShingle Pasquale D'Acunzo
Jonathan M. Ungania
Yohan Kim
Bryana R. Barreto
Steven DeRosa
Monika Pawlik
Stefanie Canals‐Baker
Hediye Erdjument‐Bromage
Audrey Hashim
Chris N. Goulbourne
Thomas A. Neubert
Mariko Saito
Henry Sershen
Efrat Levy
Cocaine perturbs mitovesicle biology in the brain
Journal of Extracellular Vesicles
cocaine
exosome
extracellular vesicle
microvesicle
mitochondria
mitophagy
title Cocaine perturbs mitovesicle biology in the brain
title_full Cocaine perturbs mitovesicle biology in the brain
title_fullStr Cocaine perturbs mitovesicle biology in the brain
title_full_unstemmed Cocaine perturbs mitovesicle biology in the brain
title_short Cocaine perturbs mitovesicle biology in the brain
title_sort cocaine perturbs mitovesicle biology in the brain
topic cocaine
exosome
extracellular vesicle
microvesicle
mitochondria
mitophagy
url https://doi.org/10.1002/jev2.12301
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