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细胞外囊泡介导的线粒体递送:前提与前景。

Extracellular vesicle-mediated mitochondria delivery: Premise and promise.

作者信息

Manickam Devika S, Pinky Paromita Paul, Khare Purva

机构信息

Department of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA, USA.

出版信息

J Cereb Blood Flow Metab. 2025 Jun 11:271678X251349304. doi: 10.1177/0271678X251349304.

Abstract

Mitochondrial transfer is highly significant under physiological as well as pathological states given the emerging recognition of mitochondria as cellular "processors" akin to microchip processors that control the operation of a mobile device. Mitochondria play indispensable roles in healthy functioning of the brain, the organ with the highest energy demand in the human body and therefore, loss of mitochondrial function plays a causal role in multiple brain diseases. In this review, we will discuss various aspects of extracellular vesicle ()-mediated mitochondrial transfer and their effects in increasing recipient cell/tissue bioenergetics with a focus on these processes in cells. A subset of EVs with particle diameters >200 nm, referred to as medium-to-large EVs (), are known to entrap mitochondria during EV biogenesis. The entrapped mitochondria are likely a combination of either polarized, depolarized mitochondria or a mixture of both. We will also discuss engineering approaches to control the of mitochondria entrapped in the m/lEVs. Controlling mitochondrial quality can allow for optimizing/maximizing the therapeutic potential of m/lEV mitochondria-a novel drug with immense potential to treat a wide range of disorders associated with mitochondrial dysfunction.

摘要

鉴于线粒体作为类似于控制移动设备运行的微芯片处理器的细胞“处理器”这一认识的不断涌现,线粒体转移在生理和病理状态下都具有高度重要性。线粒体在大脑的健康功能中发挥着不可或缺的作用,大脑是人体中能量需求最高的器官,因此,线粒体功能丧失在多种脑部疾病中起着因果作用。在这篇综述中,我们将讨论细胞外囊泡(EV)介导的线粒体转移的各个方面及其在增加受体细胞/组织生物能量学方面的作用,重点关注这些过程在细胞中的情况。已知直径大于200nm的一部分细胞外囊泡,称为中到大细胞外囊泡(m/lEV),在囊泡生物发生过程中会包裹线粒体。包裹的线粒体可能是极化线粒体、去极化线粒体或两者的混合物。我们还将讨论控制包裹在m/lEV中的线粒体质量的工程方法。控制线粒体质量可以优化/最大化m/lEV线粒体的治疗潜力——这是一种具有巨大潜力的新型药物,可治疗与线粒体功能障碍相关的广泛疾病。

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