Nikoletopoulou Vassiliki, Tavernarakis Nektarios
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Greece.
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Greece.
Methods Enzymol. 2014;545:127-55. doi: 10.1016/B978-0-12-801430-1.00006-8.
Similar to other organisms, necrotic cell death in the nematode Caenorhabditis elegans is manifested as the catastrophic collapse of cellular homeostasis, in response to overwhelming stress that is inflicted either in the form of extreme environmental stimuli or by intrinsic insults such as the expression of proteins carrying deleterious mutations. Remarkably, necrotic cell death in C. elegans and pathological cell death in humans share multiple fundamental features and mechanistic aspects. Therefore, mechanisms mediating necrosis are also conserved across the evolutionary spectrum and render the worm a versatile tool, with the capacity to facilitate studies of human pathologies. Here, we overview necrotic paradigms that have been characterized in the nematode and outline the cellular and molecular mechanisms that mediate this mode of cell demise. In addition, we discuss experimental approaches that utilize C. elegans to elucidate the molecular underpinnings of devastating human disorders that entail necrosis.
与其他生物类似,线虫秀丽隐杆线虫中的坏死性细胞死亡表现为细胞稳态的灾难性崩溃,这是对极端环境刺激形式施加的压倒性压力或内在损伤(如携带有害突变的蛋白质表达)的反应。值得注意的是,秀丽隐杆线虫中的坏死性细胞死亡与人类的病理性细胞死亡具有多个基本特征和机制方面。因此,介导坏死的机制在整个进化谱系中也是保守的,使线虫成为一种多功能工具,有能力促进对人类病理学的研究。在这里,我们概述了线虫中已被表征的坏死模式,并概述了介导这种细胞死亡模式的细胞和分子机制。此外,我们讨论了利用秀丽隐杆线虫阐明导致坏死的毁灭性人类疾病分子基础的实验方法。