Microbial Siderophore Enterobactin Promotes Mitochondrial Iron Uptake and Development of the Host via Interaction with ATP Synthase.
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.
['Qi|Bin|B|', 'Han|Min|M|']
D000255:Adenosine Triphosphate D000818:Animals D025243:Bacterial Proton-Translocating ATPases D001692:Biological Transport D017173:Caenorhabditis elegans D029742:Caenorhabditis elegans Proteins D004758:Enterobactin D004926:Escherichia coli D029968:Escherichia coli Proteins D057809:HEK293 Cells D006801:Humans D007501:Iron D008928:Mitochondria D017262:Siderophores
labile iron pool ATP-1 ATP-2 ATP5A1 E. coli Lipocalin2 enterobacteria gut microbes iron deficiency tug of war for iron