Howard Hughes Medical Institute and Department of MCDB of University of Colorado at Boulder, Boulder, CO 80309, USA.
Howard Hughes Medical Institute and Department of MCDB of University of Colorado at Boulder, Boulder, CO 80309, USA.
Cell. 2018 Oct 4;175(2):571-582.e11. doi: 10.1016/j.cell.2018.07.032. Epub 2018 Aug 23.
Elucidating the benefits of individual microbiota-derived molecules in host animals is important for understanding the symbiosis between humans and their microbiota. The bacteria-secreted enterobactin (Ent) is an iron scavenging siderophore with presumed negative effects on hosts. However, the high prevalence of Ent-producing commensal bacteria in the human gut raises the intriguing question regarding a potential host mechanism to beneficially use Ent. We discovered an unexpected and striking role of Ent in supporting growth and the labile iron pool in C. elegans. We show that Ent promotes mitochondrial iron uptake and does so, surprisingly, by binding to the ATP synthase α subunit, which acts inside of mitochondria and independently of ATP synthase. We also demonstrated the conservation of this mechanism in mammalian cells. This study reveals a distinct paradigm for the "iron tug of war" between commensal bacteria and their hosts and an important mechanism for mitochondrial iron uptake and homeostasis.
阐明宿主动物中个体微生物群衍生分子的益处对于理解人类与其微生物群之间的共生关系非常重要。细菌分泌的肠杆菌素（Ent）是一种铁掠夺性的铁载体，据推测对宿主有负面影响。然而，在人类肠道中，产肠杆菌素的共生菌的高流行率提出了一个有趣的问题，即宿主是否存在一种潜在的机制来有益地利用 Ent。我们发现 Ent 在支持秀丽隐杆线虫生长和不稳定铁池方面具有意想不到的显著作用。我们表明 Ent 促进线粒体铁摄取，令人惊讶的是，它通过与位于线粒体内部且独立于 ATP 合酶的 ATP 合酶α亚基结合来实现这一点。我们还证明了这种机制在哺乳动物细胞中的保守性。这项研究揭示了共生菌与其宿主之间“铁拉锯战”的一个独特范例，以及线粒体铁摄取和动态平衡的一个重要机制。
