One of our two current research areas involves iron metabolism in mitochondria. The iron imported into these organelles is assembled into iron-sulfur clusters and heme prosthetic groups. Some of these centers are exported into the cytosol, while others are installed into mitochondrial apo-proteins. All of these processes are regulated in healthy cells, but various genetic mutations giving rise to diseases can cause iron to accumulate (e.g. Friedreich's ataxia) or become depleted (e.g. Sideroblastic anemia). We have developed a biophysical approach involving Mossbauer, electron paramagnetic resonance, and electronic absorption spectroscopy, to study the entire iron content of intact mitochondria in healthy and genetically altered cells. This Systems Biology approach allows us to characterize the "iron-ome" of mitochondria at an unprecedented level of detail. We are also using analytical tools (e.g. liquid chromatography) to identify complexes that are involved in "trafficking" iron into and out of the organelle.
Our other research area involves mathematical modeling of cellular self-replication on the mechanistic biochemical level. We collaborate on this multidisciplinary NSF-sponsored project with a mathematician at the University of Houston (Professor Jeffrey Morgan). We have developed a modeling framework that facilitates such modeling efforts, and have designed a number of very simple and symbolic in silico cells that exhibit self-replicative behavior. Our minimal in silico cell model includes just 5 components and 5 reactions. A second generation model includes a more realistic mechanism of mitotic regulation. One novel aspect of our approach is that cellular concentration dynamics impact (and are impacted by) cellular geometry. By minimizing membrane bending energies, we are now calculating cell geometry during growth and division. Our results suggest that the "pinching" observed in real cells is enforced by cytoskeletal structures.
- Nguyen, T. Q., Kim, J. E., Brawley, H. N., & Lindahl, P. A. (2020). Chromatographic detection of low-molecular-mass metal complexes in the cytosol of Saccharomyces cerevisiae. Metallomics. 12(7), 1094-1105.
- Wofford, J. D., & Lindahl, P. A. (2019). A mathematical model of iron import and trafficking in wild-type and Mrs3/4ΔΔ yeast cells. BMC SYSTEMS BIOLOGY. 13(1), 23.
- Soma, S., Morgada, M. N., Naik, M. T., Boulet, A., Roesler, A. A., Dziuba, N., ... Gohil, V. M. (2019). COA6 Is Structurally Tuned to Function as a Thiol-Disulfide Oxidoreductase in Copper Delivery to Mitochondrial Cytochrome c Oxidase. Cell Reports. 29(12), 4114-4126.e5.
- Lindahl, P. A. (2019). A comprehensive mechanistic model of iron metabolism in Saccharomyces cerevisiae. Metallomics. 11(11), 1779-1799.
- Dziuba, N., Hardy, J., & Lindahl, P. A. (2019). Low-molecular-mass iron complexes in blood plasma of iron-deficient pigs do not originate directly from nutrient iron. Metallomics. 11(11), 1900-1911.
- Chakrabarti, M., & Lindahl, P. A. (2017). 6. The utility of Mössbauer spectroscopy in eukaryotic cell biology and animal physiology. Characterization, Properties and Applications. (pp. 163-190). De Gruyter.
- Chakrabarti, M., & Lindahl, P. A. (2014). 4. The utility of Mössbauer spectroscopy in eukaryotic cell biology and animal physiology. Iron-Sulfur Clusters in Chemistry and Biology. (pp. 49-76). De Gruyter.
- Lindahl, P. A., & Graham, D. E. (2007). Acetyl‐coenzyme A Synthases and Nickel‐Containing Carbon Monoxide Dehydrogenases. Nickel and Its Surprising Impact in Nature. (pp. 357-415). John Wiley & Sons, Ltd.
- Dziuba, N., Hardy, J., & Lindahl, P. A. (2017). SPECIATION OF NON-TRANSFERRIN BOUND IRON IN BLOOD PLASMA OF IRON DEFICIENT SWINE. AMERICAN JOURNAL OF HEMATOLOGY. 92(8), E317-E317.
- Wofford, J. D., Park, J., McCormick, S. P., Chakrabarti, M., & Lindahl, P. A. (2016). Ferric ions accumulate in the walls of metabolically inactivating Saccharomyces cerevisiae cells and are reductively mobilized during reactivation. Metallomics. 8(7), 692-708.
- Cockrell, A. L., Lindahl, P. A., Holmes-Hampton, G. P., McCormick, S. P., & Chakrabarti, M. (2013). Mossbauer and EPR studies of iron in vacuoles Iiolated from S. cerevisiae. ACS National Meeting Book of Abstracts. 245,
- Moore, M. J., Williams, N., Holmes-Hampton, G., Jhurry, N., Cockrell, A., McCormick, S., & Lindahl, P. A. (2011). Redox states of heme centers in anaerobically-isolated mitochondria from Saccharomyces cerevisiae. ACS National Meeting Book of Abstracts. 241,
- Lindahl, P. A., Bramlett, M., Tan, X. S., & Kim, E. J. (2003). Acetyl-coenzyme A synthase/carbon monoxide dehydrogenase: An enzyme with novel transition-metal-sulfide clusters and an organometallic mechanism.. ACS National Meeting Book of Abstracts. 225, U85-U85.
- Wofford, Joshua D (2018-12). Use of Mathematical Modeling and Other Biophysical Methods for Insights into Iron-Related Phenomena of Biological Systems. (Doctoral Dissertation)
- Moore, Michael John (2017-08). An Integrative Biophysical and Bioanalytical Approach for Investigating the Mitochondrial Labile Iron Pool. (Doctoral Dissertation)
- McCormick, Sean P. (2014-12). The Application of LC-ICP-MS to Study Metal Ion Homeostasis in Biological Systems. (Doctoral Dissertation)
- Park, Jinkyu (2013-12). Exploring Iron Metabolism and Regulation in Saccharomyces cerevisiae Using an Integrative Biophysical and Bioanalytical Approach. (Doctoral Dissertation)
- Cockrell, Allison Leigh (2013-12). Investigating the Roles of Vacuoles in Iron Trafficking in Saccharomyces cerevisiae. (Doctoral Dissertation)