Visualization of cyclosporin A and Ca2+-sensitive cyclical mitochondrial depolarizations in cell culture

被引:49
作者
Fall, CP
Bennett, JP
机构
[1] Univ Virginia, Hlth Sci Ctr, Ctr Study Neurodegenerat Dis, Charlottesville, VA 22908 USA
[2] Univ Virginia, Hlth Sci Ctr, Dept Neurol, Charlottesville, VA 22908 USA
[3] Univ Virginia, Hlth Sci Ctr, Dept Behav Med, Charlottesville, VA 22908 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS | 1999年 / 1410卷 / 01期
关键词
mitochondrial membrane potential; permeability transition pore; cyclosporin A; calcium dependent depolarization;
D O I
10.1016/S0005-2728(98)00177-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mitochondria not only facilitate chemiosmotic energy transduction, but also are excitable organelles that are important participants in intracellular Ca2+ signaling and are obligate participants in the active cell death cascade known as apoptosis. Underlying these functions is the cyclosporin A (CSA)-sensitive mitochondrial permeability transition pore (MTP), which can open transiently in a low conductance mode (MTPL) to relieve excess Ca2+, and irreversibly during the initiation of apoptosis. Here we image for the first time CSA- and Ca2+-sensitive cyclical mitochondrial depolarizations in cultures of the SH-SY5Y human neuroblastoma cell. In addition, we show that mitochondrial transmembrane potential (Delta Psi) increases in response to CSA, indicating a baseline channel activity. Moreover, networks of mitochondria are shown to behave as an excitable system that may use Ca2+ as a diffusible messenger to recruit neighboring mitochondria to depolarize. We propose that these depolarizations represent MTPL activity. Our data further reinforce the notion that mitochondria are excitable organelles and suggest coordinated activation of MTPL. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:77 / 84
页数:8
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