Synchronism in mitochondrial ROS flashes, membrane depolarization and calcium sparks in human carcinoma cells.

Synchronism in mitochondrial ROS flashes, membrane depolarization and calcium sparks in human carcinoma cells.
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DOI:
10.1016/j.bbabio.2017.03.001
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发表时间:
2017-06
期刊:
Biochimica et biophysica acta. Bioenergetics
影响因子:
--
通讯作者:
Grimm M
Grimm M
中科院分区:
其他
文献类型:
--
作者:
Kuznetsov AV;Javadov S;Saks V;Margreiter R;Grimm M

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线粒体是许多细胞(包括癌细胞)中活性氧(ROS)的主要产生者。然而,线粒体 ROS (mitoROS)、线粒体膜电位 (ΔΨm) 和 Ca2+ 之间复杂的相互关系尚未完全了解。使用人类癌细胞,我们进一步强调了双相 ROS 动态: - mitoROS 逐渐增加,随后 mitoROS 闪烁。此外,我们还证明了 mitoROS 生成速率和 flash 启动时间的异质性。比较线粒体和近线粒体外信号,我们发现单个线粒体中 mitoROS 闪光的机制与线粒体通透性转换孔开放(ΔΨm 塌陷)和钙火花有关,可能涉及从同一线粒体释放的一定水平的外部 ROS 触发闪光。此外,线粒体-线粒体相互作用可以在癌细胞中产生 mitoROS 闪光和 ΔΨm 塌陷的波传播,类似于 ROS 诱导的 ROS 释放 (RIRR) 现象。我们的数据表明,在癌细胞 RIRR 中,mitoROS 闪光和线粒体去极化的激活可能涉及个体线粒体和/或邻近线粒体产生的线粒体外 ROS 的参与。这可以代表 ROS-ROS 信号传导的一般机制,并在线粒体和细胞生理学和信号传导中发挥作用。
Mitochondria are major producers of reactive oxygen species (ROS) in many cells including cancer cells. However, complex interrelationships between mitochondrial ROS (mitoROS), mitochondrial membrane potential (ΔΨm) and Ca2+ are not completely understood. Using human carcinoma cells, we further highlight biphasic ROS dynamics: - gradual mitoROS increase followed by mitoROS flash. Also, we demonstrate heterogeneity in rates of mitoROS generation and flash initiation time. Comparing mitochondrial and near-extra-mitochondrial signals, we show that mechanisms of mitoROS flashes in single mitochondria, linked to mitochondrial permeability transition pore opening (ΔΨm collapse) and calcium sparks, may involve flash triggering by certain levels of external ROS released from the same mitochondria. In addition, mitochondria-mitochondria interactions can produce wave propagations of mitoROS flashes and ΔΨm collapses in cancer cells similar to phenomena of ROS-induced ROS release (RIRR). Our data suggest that in cancer cells RIRR, activation of mitoROS flashes and mitochondrial depolarization may involve participation of extramitochondrial-ROS produced either by individual mitochondria and/or by neighboring mitochondria. This could represent general mechanisms in ROS-ROS signaling with suggested role in both mitochondrial and cellular physiology and signaling.
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