Abstract
Ferritins and bacterioferritins are iron storage proteins that represent key players in iron homeostasis. Several organisms possess both forms of ferritins, however, their relative physiological roles are less understood. Mycobacterium tuberculosis possesses both ferritin (BfrB) and bacterioferritin (BfrA), playing an essential role in its pathogenesis as reported by us earlier. This study provides insights into the role of these two proteins in iron homeostasis by employing M. tuberculosis bfr mutants. Our data suggests that BfrA is required for efficient utilization of stored iron under low iron conditions while BfrB plays a crucial role as the major defense protein under excessive iron conditions. We show that these two proteins provide protection against oxidative stress and hypoxia. Iron incorporation study showed that BfrB has higher capacity for storing iron than BfrA, which augurs well for efficient iron quenching under iron excess conditions. Moreover, iron release assay demonstrated that BfrA has 3 times superior ability to release stored iron emphasizing its requirement for efficient iron release under low iron conditions, facilitated by the presence of heme. Thus, for the first time, our observations suggest that the importance of BfrA or BfrB separately might vary depending upon the iron situation faced by the cell.
Highlights
Iron is a vital element for the growth of animals, plants as well as microorganisms
Homologue, in maintaining the basal iron homeostasis of the cells, whereas the ferritin analogue BfrB is possibly required for the quenching of excess iron to protect the cell from the iron-mediated toxicity
The removal of heme from BfrA resulted in more than 1.5 times reduction in its iron release capacity demonstrating thereby that heme could be playing an important role in the process (Fig 6A). In a pathogen such as M. tuberculosis, iron homeostasis plays a vital role. Iron storage proteins such as ferritins and bacterioferritins play an important role in maintaining cellular iron homeostasis
Summary
Iron is a vital element for the growth of animals, plants as well as microorganisms. It plays an important role in several biological processes and is essential for the activity of many enzymes involved in vital cellular functions ranging from respiration to DNA replication [1]. While the deficiency of iron is detrimental to cells, its excess is potentially toxic as it promotes Fenton reaction resulting in the generation of highly toxic hydroxyl radicals [1]. The appropriate level of iron in the cell is maintained by its homeostasis based on the iron storage as well as acquisition pathways during its excessive availability and release for the cellular functions during its shortage. Most of the aerobic organisms possess ubiquitous iron storage proteins called ferritins which are highly symmetrical molecules comprising 24 subunits arranged in an octahedral pattern giving rise to an internal cavity capable of accommodating many thousands
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