Microbial Siderophore Enterobactin Promotes Mitochondrial Iron Uptake and Development of the Host via Interaction with ATP Synthase
Open accessAbstract
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.
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Enterobactin may exert beneficial effects for the host by promoting mitochondrial iron accumulation and function.
“Of interest, enterobactin may exert beneficial effects for the host by promoting mitochondrial iron accumulation and function (Qi and Han, 2018).”
From Iron in infection and immunity (2020) · cites this paper as Qi and Han, 2018
A recent study proposes that bacterial siderophores do not only serve as iron scavengers to limit bacterial growth, but are also able to support the host's iron homeostasis.
“A recent study proposes that bacterial siderophores do not only serve as iron scavengers to limit bacterial growth, but are also able to support the host’s iron homeostasis [123].”
From Iron as a central player and promising target in cancer progression (2019) · cites this paper as [123]
Binding to the α subunit of ATP synthase, mitochondrial iron uptake is promoted by enterobactin, secreted from commensal bacteria.
“Binding to the α subunit of ATP synthase, mitochondrial iron uptake is promoted by enterobactin, secreted from commensal bacteria.”
From Iron as a central player and promising target in cancer progression (2019) · cites this paper as [123]
Synthesis of enterobactin is a dominant strategy used by E. coli to salvage iron.
“Synthesis of enterobactin (Ent), a catecholate type of siderophore, is a dominant strategy used by Escherichia coli to salvage iron ( 12–14 ).”
From YdiV regulates Escherichia coli ferric uptake by manipulating the DNA-binding ability of Fur in a SlyD-dependent manner (2020) · cites this paper as [14]
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“Synthesis of enterobactin (Ent), a catecholate type of siderophore, is a dominant strategy used by Escherichia coli to salvage iron (12–14).”
Native metabolomics for mass spectrometry-based siderophore discovery.
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- Authors
- Qi, B., & Han, M.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Han, Min
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 175
- Issue
- 2
- Pages
- 571-582.e11
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2888156757
- Cited by
- 164
- References
- 56
- Citations by year
- 2026: 16 · 2025: 22 · 2024: 20 · 2023: 22 · 2022: 19 · 2021: 19 · 2020: 24 · 2019: 20 · 2018: 2
- FWCI
- 11.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NIH (P40 OD010440)
- Howard Hughes Medical Institute
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- enterobactin, siderophores, host-microbe symbiosis, gut commensal bacteria, iron homeostasis, labile iron pool, Caenorhabditis elegans, host development, iron scavenging
- MeSH terms
- Adenosine Triphosphate, Animals, Biological Transport, Enterobactin, Escherichia coli, Humans, Iron, Mitochondria, Caenorhabditis elegans, Siderophores, Bacterial Proton-Translocating ATPases, Caenorhabditis elegans Proteins, Escherichia coli Proteins, HEK293 Cells
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