Manickam Devika S, Pinky Paromita Paul, Khare Purva
Department of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA, USA.
J Cereb Blood Flow Metab. 2025 Jun 11:271678X251349304. doi: 10.1177/0271678X251349304.
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.
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。