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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Mitochondrial 'swirls' induced by oxygen stress and in the Drosophila mutant hyperswirl.
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Mitochondrial 'swirls' induced by oxygen stress and in the Drosophila mutant hyperswirl.

机译:线粒体“漩涡”是由氧气胁迫和果蝇突变体过度漩涡引起的。

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Mitochondrial dysfunction and reactive oxygen species have been implicated in the aging process as well as a wide range of hereditary and age-related diseases. Identifying primary events that result from acute oxidative stress may provide targets for therapeutic interventions that preclude aging. By using electron microscopy, we have discovered a striking initial pattern of degeneration of the mitochondria in Drosophila flight muscle under hyperoxia (100% O2). Within individual mitochondria, the cristae become locally rearranged in a pattern that we have termed a "swirl." Serial sections through individual mitochondria reveal the reorganization of the cristae in three dimensions. The cristae involved in a swirl are deficient in respiratory enzyme cytochrome c oxidase activity, within an otherwise cytochrome c oxidase-positive mitochondrion. In addition, under hyperoxia cytochrome c undergoes a conformational change, manifested by display of an otherwise hidden epitope. The conformational change is correlated with widespread apoptotic cell death in the flight muscle, as revealed by in situ terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling. In normal flies, mitochondrial swirls accumulate slowly with age. To investigate the molecular mechanisms involved in oxygen toxicity, we conducted a genetic screen for mutants that display altered survival under hyperoxia, and we identified both sensitive and resistant mutants. We describe a mutant, hyperswirl, which displays an overabundance of swirls with associated respiratory and flight defects and a greatly reduced lifespan. Such mutants can identify genes that are needed to maintain mitochondrial homeostasis throughout the lifespan.
机译:线粒体功能障碍和活性氧物质与衰老过程以及多种遗传性和与年龄有关的疾病有关。识别由急性氧化应激引起的主要事件可能为预防衰老的治疗性干预提供目标。通过使用电子显微镜,我们发现了在高氧(100%O2)下果蝇飞行肌肉中线粒体变性的惊人初始模式。在单个线粒体内,the子以我们称为“漩涡”的模式在局部重新排列。通过单个线粒体的连续切片揭示了ista的三维重组。在其他情况下,细胞色素C氧化酶阳性的线粒体中,参与涡旋的ista呼吸呼吸酶细胞色素C氧化酶活性不足。另外,在高氧下,细胞色素c经历构象变化,其表现为显示其他隐藏的表位。如原位末端脱氧核苷酸转移酶介导的dUTP缺口末端标记所揭示的,构象变化与飞行肌中广泛的凋亡细胞死亡相关。在正常蝇中,线粒体漩涡随着年龄的增长而缓慢积累。为了研究涉及氧中毒的分子机制,我们对突变体进行了遗传筛选,这些突变体在高氧环境下显示出改变的存活率,并且鉴定了敏感和抗性突变体。我们描述了一个突变体,高涡流,它显示出漩涡过多,并伴有呼吸和飞行缺陷,寿命大大降低。这样的突变体可以识别在整个生命周期中维持线粒体稳态所需的基因。

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