title: Induction of biogenic magnetization and redox control by a component of the target of rapamycin complex 1 signaling pathway.
abstract: Most organisms are simply diamagnetic, while magnetotactic bacteria and migratory animals are among organisms that exploit magnetism. Biogenic magnetization not only is of fundamental interest, but also has industrial potential. However, the key factor(s) that enable biogenic magnetization in coordination with other cellular functions and metabolism remain unknown. To address the requirements for induction and the application of synthetic bio-magnetism, we explored the creation of magnetism in a simple model organism. Cell magnetization was first observed by attraction towards a magnet when normally diamagnetic yeast Saccharomyces cerevisiae were grown with ferric citrate. The magnetization was further enhanced by genetic modification of iron homeostasis and introduction of ferritin. The acquired magnetizable properties enabled the cells to be attracted to a magnet, and be trapped by a magnetic column. Superconducting quantum interference device (SQUID) magnetometry confirmed and quantitatively characterized the acquired paramagnetism. Electron microscopy and energy-dispersive X-ray spectroscopy showed electron-dense iron-containing aggregates within the magnetized cells. Magnetization-based screening of gene knockouts identified Tco89p, a component of TORC1 (Target of rapamycin complex 1), as important for magnetization; loss of TCO89 and treatment with rapamycin reduced magnetization in a TCO89-dependent manner. The TCO89 expression level positively correlated with magnetization, enabling inducible magnetization. Several carbon metabolism genes were also shown to affect magnetization. Redox mediators indicated that TCO89 alters the intracellular redox to an oxidized state in a dose-dependent manner. Taken together, we demonstrated that synthetic induction of magnetization is possible and that the key factors are local redox control through carbon metabolism and iron supply.
authors.affiliation: Department of Systems Biology, Harvard Medical School and the Wyss Institute of Biological Inspired Engineering, Harvard University, Boston, MA, USA.
authors.forename: Keiji
authors.initials: K
authors.lastname: Nishida
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Silver
mesh_terms: D027682:Cation Transport Proteins / Q000378:metabolism; D005290:Ferric Compounds / Q000378:metabolism; D005293:Ferritins / Q000096:biosynthesis; D018628:Gene Dosage; D055786:Gene Knockout Techniques; D006801:Humans; D033862:Iron-Binding Proteins / Q000235:genetics / Q000378:metabolism; D060328:Magnetic Phenomena; D060306:Magnetometry; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D030781:Organisms, Genetically Modified; D010084:Oxidation-Reduction; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D000096923:Frataxin
chemical_list: D027682:Cation Transport Proteins; D005290:Ferric Compounds; D005293:Ferritins; D033862:Iron-Binding Proteins; D024101:Mitochondrial Proteins; D009249:NADP; D017853:Phosphotransferases (Alcohol Group Acceptor); D017346:Protein Serine-Threonine Kinases; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000096923:Frataxin; C089360:CCC1 protein, S cerevisiae; C561842:TORC1 protein complex, S cerevisiae; C485218:Tco89 protein, S cerevisiae; C025314:ferric citrate; C071570:SNF1-related protein kinases; C060670:POS5 protein, S cerevisiae