Toward high-content screening of mitochondrial morphology and membrane potential in living cells

Toward high-content screening of mitochondrial morphology and membrane potential in living cells
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DOI:
10.1016/j.biocel.2015.01.020
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发表时间:
2015-06-01
影响因子:
4
通讯作者:
Koopman, Werner J. H.
Koopman, Werner J. H.
中科院分区:
生物学2区
文献类型:
--
作者:
Iannetti, Eligio F.;Willems, Peter H. G. M.;Koopman, Werner J. H.

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线粒体是双膜细胞器,参与各种关键的细胞过程。在专门的蛋白质机制的控制下,线粒体移动并不断融合和分裂。这些“线粒体动力学”在空间和时间上与线粒体和细胞功能状态双向相关。由于电子传递链(ETC)的作用,线粒体内膜显示出内部负膜电位(Delta psi)。后者被认为是线粒体“健康”的功能性读出,并且是维持正常线粒体ATP产生和线粒体融合所必需的。在过去的十年中,活细胞显微镜策略开发的同时定量的Δ psi和线粒体形态。这表明ETC功能障碍、Δ psi的变化和线粒体结构的畸变通常平行发生,表明它们是治疗干预的潜在靶点。在这里,我们讨论了如何结合高含量和高通量的策略,可用于分析遗传和/或药物诱导的影响,在单个细胞器,细胞和细胞popules.This文章的一部分,有针对性的问题,题为:能量代谢紊乱和治疗。(C)2015爱思唯尔有限公司版权所有。
Mitochondria are double membrane organelles involved in various key cellular processes. Governed by dedicated protein machinery, mitochondria move and continuously fuse and divide. These "mitochondrial dynamics" are bi-directionally linked to mitochondrial and cell functional state in space and time. Due to the action of the electron transport chain (ETC), the mitochondrial inner membrane displays a inside-negative membrane potential (Delta psi). The latter is considered a functional readout of mitochondrial "health" and required to sustain normal mitochondrial ATP production and mitochondrial fusion. During the last decade, live-cell microscopy strategies were developed for simultaneous quantification of Delta psi and mitochondrial morphology. This revealed that ETC dysfunction, changes in Delta psi and aberrations in mitochondrial structure often occur in parallel, suggesting they are linked potential targets for therapeutic intervention. Here we discuss how combining high-content and high-throughput strategies can be used for analysis of genetic and/or drug-induced effects at the level of individual organelles, cells and cell populations.This article is part of a Directed Issue entitled: Energy Metabolism Disorders and Therapies. (C) 2015 Elsevier Ltd. All rights reserved.