Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cell Metab. 2012 Jan 4;15(1):88-99. doi: 10.1016/j.cmet.2011.12.003.
Zinc is an essential trace element involved in many biological processes and human diseases. Because zinc deficiency and excess are deleterious, animals require homeostatic mechanisms to maintain zinc levels in response to dietary fluctuations. Here, we demonstrate that lysosome-related organelles in intestinal cells of C. elegans, called gut granules, function as the major site of zinc storage. Zinc storage in gut granules promotes detoxification and subsequent mobilization, linking cellular and organismal zinc metabolism. The cation diffusion facilitator protein CDF-2 plays a critical role in this process by transporting zinc into gut granules. In response to high dietary zinc, gut granules displayed structural changes characterized by a bilobed morphology with asymmetric distributions of zinc and molecular markers. We defined a genetic pathway that mediates the formation of bilobed morphology. These findings elucidate mechanisms of zinc storage, detoxification, and mobilization in C. elegans and may be relevant to other animals.
锌是一种必需的微量元素,参与许多生物过程和人类疾病。由于锌缺乏和过量都是有害的,动物需要通过体内平衡机制来维持锌水平,以响应饮食波动。在这里,我们证明了线虫肠道细胞中的溶酶体相关细胞器,称为肠道颗粒,是锌储存的主要部位。肠道颗粒中的锌储存促进了解毒和随后的动员,将细胞和机体的锌代谢联系起来。阳离子扩散促进因子蛋白 CDF-2 通过将锌运输入肠道颗粒在这个过程中起着关键作用。在高膳食锌的情况下,肠道颗粒显示出结构变化,表现为具有不对称分布锌和分子标记的双叶形态。我们定义了一个遗传途径,介导双叶形态的形成。这些发现阐明了线虫中锌储存、解毒和动员的机制,可能与其他动物有关。