Dept. of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, L'Aquila 67100, Italy.
Dept. of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, L'Aquila 67100, Italy.
Ageing Res Rev. 2024 Nov;101:102522. doi: 10.1016/j.arr.2024.102522. Epub 2024 Oct 5.
Mitochondria are metabolic and signalling hubs that integrate a plethora of interconnected processes to maintain cell homeostasis. They are also dormant mediators of inflammation and cell death, and with aging damages affecting mitochondria gradually accumulate, resulting in the manifestation of age-associated disorders. In addition to coordinate multiple intracellular functions, mitochondria mediate intercellular and inter-organ cross talk in different physiological and stress conditions. To fulfil this task, mitochondrial signalling has evolved distinct and complex conventional and unconventional routes of horizontal/vertical mitochondrial transfer. In this regard, great interest has been focused on the ability of extracellular vesicles (EVs), such as exosomes and microvesicles, to carry selected mitochondrial cargoes to target cells, in response to internal and external cues. Over the past years, the field of mitochondrial EVs (mitoEVs) has grown exponentially, revealing unexpected heterogeneity of these structures associated with an ever-expanding mitochondrial function, though the full extent of the underlying mechanisms is far from being elucidated. Therefore, emerging subsets of EVs encompass exophers, migrasomes, mitophers, mitovesicles, and mitolysosomes that can act locally or over long-distances to restore mitochondrial homeostasis and cell functionality, or to amplify disease. This review provides a comprehensive overview of our current understanding of the biology and trafficking of MitoEVs in different physiological and pathological conditions. Additionally, a specific focus on the role of mitoEVs in aging and the onset and progression of different age-related diseases is discussed.
线粒体是代谢和信号枢纽，整合了大量相互关联的过程，以维持细胞内稳态。它们也是炎症和细胞死亡的休眠调节剂，随着衰老损伤逐渐累积，导致与年龄相关的疾病的表现。除了协调多种细胞内功能外，线粒体还在不同的生理和应激条件下介导细胞间和器官间的交叉对话。为了完成这项任务，线粒体信号转导已经进化出独特而复杂的传统和非常规的水平/垂直线粒体转移途径。在这方面，人们对细胞外囊泡（EVs），如外泌体和微泡，在内外信号的作用下，将选定的线粒体货物转移到靶细胞的能力产生了极大的兴趣。在过去的几年中，线粒体 EVs（mitoEVs）领域呈指数级增长，揭示了这些结构与不断扩大的线粒体功能相关的出乎意料的异质性，尽管潜在机制的全部程度还远未阐明。因此，新兴的 EV 亚群包括外泌体、迁移体、线粒体体、线粒体囊泡和线粒体溶酶体，它们可以在局部或远距离发挥作用，以恢复线粒体内稳态和细胞功能，或放大疾病。本文综述了我们目前对不同生理和病理条件下 MitoEVs 的生物学和运输的理解。此外，还特别关注了 mitoEVs 在衰老以及不同与年龄相关的疾病的发生和进展中的作用。
