H2O2-induced mitochondrial fragmentation in C2C12 myocytes.

H2O2-induced mitochondrial fragmentation in C2C12 myocytes.
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DOI:
10.1016/j.freeradbiomed.2010.08.024
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发表时间:
2010-12-01
影响因子:
7.4
通讯作者:
Brooks, George A.
Brooks, George A.
中科院分区:
医学1区
文献类型:
--
作者:
Fan, Xiying;Hussien, Rajaa;Brooks, George A.

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在骨骼肌和许多其他类型的细胞中,线粒体作为一个复杂的动态网络存在,其中“个体”线粒体即使在非刺激条件下也仅短暂存在。连续的线粒体分裂和融合的平衡定义了线粒体网状结构的形态。环境刺激,如氧化应激,可以影响融合和裂变速率,导致网络连接的转变。使用C2 C12小鼠心肌细胞的共聚焦激光扫描显微镜,我们表明,急性暴露于活性氧(ROS)过氧化氢(H2 O2)诱导的线粒体网状结构的缓慢碎片,这是可逆的超过24小时。虽然H2 O2在培养基中迅速分解,但在处理后5-6小时发生完全的片段化,表明H2 O2通过调节细胞生理学影响线粒体形态。超生理浓度(>1 mM)的H2 O2具有细胞毒性,但足以诱导瞬时片段化的较低浓度(250 μM)不会降低细胞活力。H2 O2诱导的线粒体断裂之前,线粒体内膜电位和最大呼吸率的下降,这表明一种可能的机制。由于H2 O2是在收缩肌肉中产生的,我们的研究结果提高了ROS产生可能有助于运动诱导的线粒体形态变化的可能性。
In skeletal muscle and many other cell types, mitochondria exist as an elaborate and dynamic network in which “individual” mitochondria exist only transiently even under non-stimulated conditions. The balance of continuous mitochondrial fission and fusion defines the morphology of the mitochondrial reticulum. Environmental stimuli, such as oxidative stress, can influence fusion and fission rates, resulting in a transformation of the network's connectivity. Using confocal laser scanning microscopy of C2C12 mouse myocytes, we show that acute exposure to the reactive oxygen species (ROS) hydrogen peroxide (H2O2) induces a slow fragmentation of the mitochondrial reticulum that is reversible over 24 hours. Although H2O2 decomposes rapidly in culture medium, the full extent of fragmentation occurs 5-6 hours post-treatment, suggesting that H2O2 affects mitochondrial morphology by modulating cellular physiology. Supraphysiological (>1 mM) concentrations of H2O2 are cytotoxic, but lower concentrations (250 μM) sufficient to induce transient fragmentation do not lower cell viability. H2O2-induced mitochondrial fragmentation is preceded by decreases in inner mitochondrial membrane potential and maximal respiratory rate, suggesting a possible mechanism. Because H2O2 is produced in contracting muscle, our results raise the possibility that ROS generation may contribute to exercise-induced changes in mitochondrial morphology in vivo.
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