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治疗性线粒体移植的前景。

Prospects for therapeutic mitochondrial transplantation.

作者信息

Gollihue Jenna L, Rabchevsky Alexander G

机构信息

University of Kentucky, Department of Physiology and Spinal Cord & Brain Injury Research Center, Lexington, KY 40536-0509, United States.

University of Kentucky, Department of Physiology and Spinal Cord & Brain Injury Research Center, Lexington, KY 40536-0509, United States.

出版信息

Mitochondrion. 2017 Jul;35:70-79. doi: 10.1016/j.mito.2017.05.007. Epub 2017 May 19.

Abstract

Mitochondrial dysfunction has been implicated in a multitude of diseases and pathological conditions- the organelles that are essential for life can also be major players in contributing to cell death and disease. Because mitochondria are so well established in our existence, being present in all cell types except for red blood cells and having the responsibility of providing most of our energy needs for survival, then dysfunctional mitochondria can elicit devastating cellular pathologies that can be widespread across the entire organism. As such, the field of "mitochondrial medicine" is emerging in which disease states are being targeted therapeutically at the level of the mitochondrion, including specific antioxidants, bioenergetic substrate additions, and membrane uncoupling agents. New and compelling research investigating novel techniques for mitochondrial transplantation to replace damaged or dysfunctional mitochondria with exogenous healthy mitochondria has shown promising results, including tissue sparing accompanied by increased energy production and decreased oxidative damage. Various experimental techniques have been attempted and each has been challenged to accomplish successful transplantation. The purpose of this review is to present the history of mitochondrial transplantation, the different techniques used for both in vitro and in vivo delivery, along with caveats and pitfalls that have been discovered along the way. Results from such pioneering studies are promising and could be the next big wave of "mitochondrial medicine" once technical hurdles are overcome.

摘要

线粒体功能障碍与多种疾病和病理状况有关——这些对生命至关重要的细胞器也可能是导致细胞死亡和疾病的主要因素。由于线粒体在我们的生命中如此重要,存在于除红细胞外的所有细胞类型中,并负责为我们的生存提供大部分能量需求,因此功能失调的线粒体可引发毁灭性的细胞病变,这些病变可能在整个生物体中广泛存在。因此,“线粒体医学”领域正在兴起,其中针对疾病状态的治疗靶点是线粒体水平,包括特定的抗氧化剂、生物能量底物添加物和膜解偶联剂。研究用外源性健康线粒体替代受损或功能失调线粒体的线粒体移植新技术的新的、引人注目的研究已显示出有希望的结果,包括组织保护伴随着能量产生增加和氧化损伤减少。已经尝试了各种实验技术,并且每种技术在实现成功移植方面都面临挑战。本综述的目的是介绍线粒体移植的历史、用于体外和体内递送的不同技术,以及在此过程中发现的注意事项和陷阱。一旦克服技术障碍,此类开创性研究的结果很有希望,可能成为“线粒体医学”的下一个大浪潮。

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