During the summer of 2008, the radiation safety officer at Texas A&M University stopped by my lab in the Chemistry department (http://www.chem.tamu.edu/faculty/faculty_detail.php?ID=51) to inspect the Mössbauer spectrometer that I purchased last year from Janis Research and Science Engineering and Education Co (SEE Co. – formerly Web Research). During our conversation, he mentioned that he had heard that Mössbauer was a “dying technique”. I must say that I found this perception amusing since Mössbauer spectroscopy has recently become our central research tool and is providing us with unprecedented insights into the metabolism of iron in mitochondria and indeed in whole cells. Since our instrument was installed by Dr. Tom Kent in December 2008, we have used it continuously – 24/7. Indeed, its utility has been beyond our expectations such that we now plan to purchase a second instrument. About 2002, I became interested in systems biology – an emerging field that complements the more traditional biochemical approach of disrupting a cell, purifying a protein, and then studying it using, for example, Mössbauer spectroscopy. Indeed, for the past 20 years, and in collaboration with Dr. Eckard Münck (Carnegie-Mellon University), I have conducted research in this way on the Ni-Fe-S containing enzyme acetyl-CoA synthase/carbon monoxide dehydrogenase. In systems biology, one studies an intact system– in our case the mitochondrion, an organelle often called the “powerhouse” of the cell - in all of its glorious complexity. By applying Mössbauer spectroscopy to an entire organelle, we can see all of the 57Fe in the organelle, and in proportion to the amounts present. Thus, for the first time, we determined the proportion of mitochondrial Fe present as [Fe4S4] clusters, [Fe2S2] clusters, heme Fe, and most interestingly, nonheme mononuclear Fe (see Ref 1). This last species has been especially difficult to track by other methods; but by using

Dr. Lindahl and graduate student Ren Miao admiring our Mössbauer instrument.   4.2 K Mössbauer spectra of isolated mitochondria from cells replete (A) and depleted (B and C) in a ferredoxin that is required for Fe/S cluster and heme biosynthesis. In (C), nonheme mononuclear ferrous ions have been oxidized by the O2 in the growth medium, accumulating as aggregated ferric nanoparticles.  Figure adapted from ref 2.

The spectrum shown reveals aggregated ferric nanoparticles in a sample that mimics one such diseased state. Our future plans are to better understand Fe trafficking in cells and to understand on a mechanistic level why Fe accumulates in these diseased states. In all of these studies, I have no doubt that Mössbauer spectroscopy will play a central role, and I thank both Tom Kent of SEE Co, and Janis Research, for manufacturing these incredible instruments.
References

• “Electron paramagnetic resonance and Mössbauer spectroscopy of intact mitochondria from respiring Saccharomyces cerevisiae” Brandon N. Hudder, Jessica Garber Morales, Audria A. Stubna, Eckard Münck, Michael P. Hendrich, and Paul A. Lindahl, 2007, J. Biol. Inorg. Chem. 12, 1029-1053.
• EPR and Mössbauer Spectroscopy of Intact Mitochondria Isolated from Yah1p-depleted Saccharomyces cerevisiae” Ren Miao, Marlène Martinho, Jessica Garber Morales, Hansoo Kim, E. Ann Ellis, Roland Lill, Michael P. Hendrich, Eckard Münck and Paul A. Lindahl, 2008 Biochemistry, 47, 9888-9899