The iron-sulfur cluster of bacterioferritin-associated ferredoxin (Bfd): A ‘biological fuse’ that prevents oxidative damage to cells?

Bradley, Justin M., Carter, Aiden M., Bugg, Zinnia, Andrews, Simon C. and Le Brun, Nick E. (2025) The iron-sulfur cluster of bacterioferritin-associated ferredoxin (Bfd): A ‘biological fuse’ that prevents oxidative damage to cells? Angewandte Chemie International Edition. ISSN 1433-7851 (In Press)

Microsoft Word (OpenXML) (Bfd FeS fuse MS re-revised unmarked) - Accepted Version Restricted to Repository staff only until 31 December 2099. Request a copy

Abstract

Iron is in an essential micronutrient in living systems. However, it is also potentially toxic and so the concentration of chelatable iron within cells is tightly regulated to prevent catalytic formation of harmful reactive oxygen species (ROS). Ferritins play a key role in iron homeostasis by storing excess iron as an insoluble ferric mineral within the protein. When bacterial cells become iron deficient, this store may be accessed by reduction/solubilisation of the iron. Bacterioferritins utilise heme, bound at an inter-subunit site, to support electron transfer to the stored mineral. Electrons for heme reduction are shuttled from NADPH via Bfd, a [2Fe-2S] cluster-containing ferredoxin. This raises the paradox that the synthesis of an iron-dependent protein cofactor is required under conditions of iron-deficiency so that stored iron can be utilised. Here we show that exposure of Bfd to ROS suppresses the capacity of the protein to stimulate iron release from bacterioferritin. We propose that reliance of iron release on Bfd evolved to ensure that chelatable iron levels do not increase under oxidative stress conditions. Thus, the Bfd iron-sulfur cluster functions as a ‘biological fuse’ in providing a fail-safe that immediately halts iron release once ROS accumulate to damaging concentrations.

Item Type:	Article
Additional Information:	Data Availability Statement: All data are available from the corresponding authors upon request. Funding Information: We thank UEA for supporting JMB’s position and the award of a PhD studentship to ZB.
Faculty \ School:	Faculty of Science > School of Chemistry, Pharmacy and Pharmacology Faculty of Science
UEA Research Groups:	Faculty of Science > Research Groups > Chemistry of Life Processes Faculty of Science > Research Centres > Centre for Molecular and Structural Biochemistry
Depositing User:	LivePure Connector
Date Deposited:	17 Jun 2025 13:30
Last Modified:	17 Jun 2025 13:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/99580
DOI:	issn:1433-7851

Actions (login required)

View Item