Program in Systems Biology and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Andalusian Center for Developmental Biology, Consejo Superior de Investigaciones Científicas, Junta de Andalucía, Universidad Pablo de Olavide, Department of Molecular Biology and Biochemical Engineering, 41013 Seville, Spain.
Cell Host Microbe. 2019 Sep 11;26(3):400-411.e3. doi: 10.1016/j.chom.2019.07.010. Epub 2019 Aug 20.
Iron is an essential micronutrient for all forms of life; low levels of iron cause human disease, while too much iron is toxic. Low iron levels induce reactive oxygen species (ROS) by disruption of the heme and iron-sulfur cluster-dependent electron transport chain (ETC). To identify bacterial metabolites that affect development, we screened the Keio Escherichia coli collection and uncovered 244 gene deletion mutants that slow Caenorhabditis elegans development. Several of these genes encode members of the ETC cytochrome bo oxidase complex, as well as iron importers. Surprisingly, either iron or anti-oxidant supplementation reversed the developmental delay. This suggests that low bacterial iron results in high bacterial ROS and vice versa, which causes oxidative stress in C. elegans that subsequently impairs mitochondrial function and delays development. Our data indicate that the bacterial diets of C. elegans provide precisely tailored amounts of iron to support proper development.
铁是所有生命形式必需的微量元素;铁含量低会导致人类疾病,而铁含量过高则有毒。铁水平降低会通过破坏血红素和铁硫簇依赖的电子传递链 (ETC) 来诱导活性氧 (ROS)。为了鉴定影响发育的细菌代谢物,我们筛选了 Keio 大肠杆菌文库,发现了 244 个基因缺失突变体,这些突变体减缓了秀丽隐杆线虫的发育。这些基因中的几个编码 ETC 细胞色素 bo 氧化酶复合物以及铁摄取体的成员。令人惊讶的是,铁或抗氧化剂的补充都能逆转发育迟缓。这表明低细菌铁导致高细菌 ROS,反之亦然,这会导致秀丽隐杆线虫的氧化应激,从而随后损害线粒体功能并延迟发育。我们的数据表明,秀丽隐杆线虫的细菌饮食提供了精确调整的铁含量,以支持其正常发育。