Iron is the most essential nutrient, but highly toxic when it’s free and in excess. Therefore, iron concentration is tightly regulated by Nature in almost all organisms using intracellular ferritin protein, for sequestration and repository purposes. Ferritin proteins are hollow, symmetrical, nanocaged spherical structures, self-assembled from 24-subunits and can accommodate up to 4500 iron atoms, unlike 4 atoms in haemoglobin. Iron enters the ferritin nanocavity through hydrophilic ion channels/pores where it undergoes rapid oxidation and bio-mineralization via protein-mediated ferroxidase activity and hydrolytic processes. In human, about 1/4th of total body iron is safely stored inside ferritin nano cavity.
Our lab focuses on the following key research areas :
Mechanism and Regulation of Ferritin Iron Release: When required, ferritin caged iron is used for cell metabolism such as synthesis of haemoglobin, DNA and ATP, but the process and rate of iron release in response to cellular requirement remains an unsolved puzzle.
Functional Role of Heme in Bacterial Ferritins: Bacterioferritins differ structurally from other members of the ferritin superfamily in terms of possessing a heme binding site at each of its 12 subunit−dimer interfaces. The functional role of heme in bacterial ferritins, and whether/how? it influences iron storage, mobilization, and redox activity of ferritin is unknown.
Physiological Significance of Phosphate in Ferritin Iron Mineral: Ferritin iron mineral from bacteria/plant contains relatively higher phosphate content (Fe:P ̴ 1-2) compared to animals (Fe:P ̴ >10). It is unknown whether this large phosphate content in ferritin mineral has any physiological significance or it is just a coincidence (with phosphate rich environment in soil/plastids) or a consequence of plant/microbial physiology or due to variable ferritin pore electrostatics.
Biomedical Applications of the Ferritin Cage: High thermal/chemical stability, nanosized cavity, metal ion scavenging ability, and the reversible disassembly/reassembly property of the ferritin cage makes it a promising candidate for biomedical applications. Its potential spans drug and gene delivery, bioimaging, and vaccine development, offering novel therapeutic and diagnostic strategies.
Selected publications
Rational pore engineering reveals the relative contribution of enzymatic sites and self-assembly towards rapid ferroxidase activity and mineralization: Impact of electrostatic guiding and cage-confinement in bacterioferritin
Parida A., Bhattacharyya G., Mallik S., Behera, R. K*.
Chemical Science; 2025, 16, 3978-3997.
Gastric stability of bare & chitosan-fabricated ferritin and its bio-mineral: Implication towards potential dietary iron supplement (HOT article by RSC)
Raut R. K., Bhattacharyya G., Behera, R. K*.
Dalton Transactions; 2024, 53, 13815-13830.
Iron Mobilization from Intact Ferritin: Effect of Differential Redox Activity of Quinone Derivatives with NADH/O2 and In Situ Generated ROS
Behera N., Bhattacharyya G., Behera S., Behera, R. K*.
Journal of Biological Inorganic Chemistry; 2024, 29(4), 455-475.
Alteration of Coaxial Heme Ligands Reveals the Role of Heme in Bacterioferritin from Mycobacterium tuberculosis
Mohanty A., Parida A., Subhadarshanee B., Behera, N., Subudhi, T., Koochana P. K., Behera, R.K*.
Inorganic Chemistry; 2021, 60(22), 16937-16952.
Kinetics of Ferritin Self-assembly by Laser Light Scattering: Impact of Subunit Concentration, pH and Ionic Strength
Mohanty A., Mithra K., Jena SS, Behera, R.K*.
Biomacromolecules; 2021, 22(4), 1389-1398.
Impact of Phosphate on Iron Mineralization and Mobilization in Non-heme Bacterioferritin B from Mycobacterium tuberculosis
Parida, A; Mohanty, A; Kansara, B; Behera, R.K*.
Inorganic Chemistry; 2020, 59(1), 629-641.
Iron Mineralizing Bacterioferritin A from Mycobacterium tuberculosis exhibits Unique Catalase-Dps like Dual Activities
Mohanty, A; Subhadarshanee, B; Barman, P; Mahapatra, C; Aishwarya, B.; Behera, R.K*.
Inorganic Chemistry; 2019, 58(8), 4741-4752.
15. “Releasing Iron from Ferritin Protein Nanocage by Reductive Method: The Role of Electron Transfer Mediator.”
Koochana PK, Mohanty A, Das S, SubhadarshaneeB, Satpati S, Dixit A, Sabat SC, Behera R.K*.
Biochimica et Biophysica Acta (BBA) – General Subjects.; 2018, 1862, 1190-1198.
Surface Charge Dependent Separation of Modified and Hybrid Ferritin in Native PAGE: Impact of Lysine 104
Subhadarshanee B, Mohanty A, Jagdev MK, Vasudevan D, Behera R.K*.
Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics; 2017, 1865, 1267-73.