# Iron Trafficking and Regulation in Biological Systems

> **NIH NIH R35** · TEXAS A&M UNIVERSITY · 2021 · $346,571

## Abstract

Project Summary/Abstract
The PI requests support of his research program in Iron Trafficking and Regulation in Biological
Systems. Using powerful biophysical, bioanalytical, and mathematical tools, the PI and his
coworkers propose to characterize and quantify the major iron species in isolated organelles,
whole cells and organs from a wide diversity of biological systems. Mössbauer spectroscopy will
be the primary biophysical tool, with EPR and UV-vis spectroscopies playing supporting roles.
Various genetic strains of budding yeast and human cells will be enriched in 57Fe. Mitochondria,
cytosol, vacuoles and other organelles will be isolated. The major Fe species in these cellular
components will be probed. Ordinary-differential-equations-based mathematical models will be
developed to analyze the results obtained and to generate a system’s level description of Fe
trafficking and regulation. No other group worldwide investigates Fe in this way. Yeast strains
are being investigated in which Mrs3/4, high-affinity Fe importers located on the mitochondrial
inner membrane, have been deleted and overexpressed. Other Fe-associated yeast strains, as
well as human Jurkat cells in which mitoferrins (homologs of Mrs3/4) and ferritin are knocked-
down, will also be investigated. The Fe content of Escherichia coli and other prokaryotes will be
similarly explored. The central bioanalytical tool will be a liquid chromatography system located
in a refrigerated anaerobic glove box that is linked to an on-line inductively coupled plasma
mass spectrometer AND to an on-line electrospray ionization mass spectrometer. This LC-
(ICP)-ESI-MS system will be unique worldwide. It will be used to characterize dozens of labile
low-molecular-mass (LMM) metal complexes that the PI and his group have discovered in
organelles, cytosol, blood plasma, and in E. coli. A LMM Fe complex in mitochondria that has a
mass of ca. 580 Da (called Fe580) is actively under investigation. Fe580 is most probably used as
feedstock for iron-sulfur cluster (ISC) assembly and for the iron-insertion step of heme
biosynthesis. The composition of a LMM sulfur-containing species called X-S will also be
investigated. X-S is exported from mitochondria in association with ISC assembly, and it may be
used to assemble cytosolic ISCs and to regulate Fe trafficking. A LMM Fe species in blood
plasma called “non-transferrin-bound iron” or NTBI will be investigated using pigs into which a
feeding tube and sampling catheters have been surgically implanted. NTBI damages organs in
patients with Fe-overload diseases such as hemochromatosis. Various strains of mice with Fe-
associated diseases will be investigated to determine the form of Fe that accumulates in their
organs. The effect of hypoxia on Fe accumulation will also be examined.

## Key facts

- **NIH application ID:** 10173833
- **Project number:** 5R35GM127021-04
- **Recipient organization:** TEXAS A&M UNIVERSITY
- **Principal Investigator:** PAUL A. LINDAHL
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $346,571
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10173833

## Citation

> US National Institutes of Health, RePORTER application 10173833, Iron Trafficking and Regulation in Biological Systems (5R35GM127021-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10173833. Licensed CC0.

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