Functionally and morphologically damaged mitochondria observed in auditory cells under senescence-inducing stress.
Functionally and morphologically damaged mitochondria observed in auditory cells under senescence-inducing stress.
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DOI：
10.1038/s41514-017-0002-2
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发表时间：
2017
影响因子：
5
通讯作者：
Yamasoba T
中科院分区：
文献类型：
--
作者：
Kamogashira T;Hayashi K;Fujimoto C;Iwasaki S;Yamasoba T
目的探讨听觉细胞早衰模型中线粒体功能的变化。短时间暴露于H2O2 （1 h, 0.1 mM）可诱导Corti 1型内耳听觉器官细胞过早衰老。透射电镜分析显示，短时间接触H2O2后，听觉细胞出现线粒体和含有致密细胞器的自噬体损伤。在h2o2处理的细胞中，线粒体骨架图像的分支和连接参数显著降低。在h2o2处理的细胞中，一个分枝的小管网形成不良，具有许多微小簇和少数相对较大的实体共存的特点。在生物能学方面，h2o2处理导致听细胞线粒体膜电位呈剂量依赖性降低。碎片化的线粒体（融合<裂变）处于低电位。此外，高灌注线粒体的电位（融合>裂变）略低于对照细胞。活体听觉细胞短时间暴露于H2O2会损伤线粒体呼吸能力，但对基线ATP生成率没有影响。H2O2处理后，线粒体膜电位对解偶联剂的易损性增加。我们的研究结果表明，由耗氧量下降引起的线粒体功能障碍应该是听觉细胞过早衰老过程的第一个事件，导致线粒体融合/裂变失衡，线粒体网络崩溃。线粒体形态和生理影响老年性听力损失的发生过程。东京大学Tatsuya Yamasoba教授的研究小组研究了听觉细胞系在氧化应激诱导的过早衰老下，线粒体在呼吸功能、膜电位和形态方面的功能变化。形态学和功能性线粒体损伤表现为呼吸能力不足和融合/裂变平衡的波动。这些结果为听觉细胞早衰过程中线粒体代谢活动及其网络结构之间的基本相互依赖提供了证据。这是一项揭示线粒体动力学和呼吸系统对听觉细胞过早衰老过程影响的开创性研究。进一步研究细胞间通讯，包括细胞骨架和细胞核，可以帮助我们了解老年性听力损失的病因。
We aimed at determining the mitochondrial function in premature senescence model of auditory cells. Short exposure to H2O2 (1 h, 0.1 mM) induced premature cellular senescence in House Ear Institute-Organ of Corti 1 auditory cells. The transmission electron microscopy analysis revealed that damaged mitochondria and autophagosomes containing dense organelles appeared in the auditory cells after short exposure to H2O2. The branch and junction parameters of the skeletonized image of the mitochondria were found to decrease significantly in H2O2-treated cells. A branched reticulum of tubules was poorly formed, featuring coexistence of numerous tiny clusters along with few relatively large entities in the H2O2-treated cells. In terms of bioenergetics, H2O2-treatment led to the dose-dependent decrease in mitochondrial membrane potential in the auditory cells. The fragmented mitochondria (fusion < fission) were in a low potential. In addition, the potential of hyperfused mitochondria (fusion > fission) was slightly lower than the control cells. The short-time exposure of live auditory cells to H2O2 damaged the mitochondrial respiratory capacity without any effect on the baseline ATP production rates. The vulnerability of the mitochondrial membrane potential to the uncoupling reagent was increased after H2O2 treatment. Our findings indicated that the mitochondrial dysfunction due to the decline in the O2 consumption rate should be the first event of premature senescence process in the auditory cells, resulting in the imbalance of mitochondrial fusion/fission and the collapse of the mitochondrial network. The mitochondrial morphology and physiology could influence the process of age-related hearing loss. Prof. Tatsuya Yamasoba’s research group at the University of Tokyo has examined the functional changes of mitochondria in terms of its respiratory function, membrane potential and morphology under premature senescence induced by oxidative stress in an auditory cell line. The morphological and functional mitochondrial damage were observed as the respiratory capacity deficiency and the fluctuation of the fusion/fission balance. Their results provide evidence of the fundamental interdependence between mitochondrial metabolic activity and its network structure in premature senescence process of auditory cells. This is a pioneer study to indicate the influence of mitochondrial dynamics and respiratory system on the premature senescence process of auditory cells. Further studies into inter cellular communication including cytoskeleton and nucleus can help us understand the etiology underlying age-related hearing loss.