Life-On-Hold: Lanthanoids Rapidly Induce a Reversible Ametabolic State in Mammalian Cells
1
Research Institute of Eye Diseases, 119021 Moscow, Russia
2
Institute of Fundamental Medicine and Biology, Kazan Federal University, 420111 Kazan, Russia
3
Prokhorov General Physics Institute of the Russian Academy of Sciences, 119991 Moscow, Russia
4
Kazan Science Centre, Kazan Institute of Biochemistry and Biophysics, Russian Academy of Sciences, 420111 Kazan, Russia
5
Laboratory of Molecular Microbiology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia
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Institute for Regenerative Medicine, Lomonosov State University, 119991 Moscow, Russia
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Endocrinology Research Center, 115478 Moscow, Russia
8
Laboratory of Orphan Diseases, Moscow Institute of Physics and Technology, 141701 Moscow, Russia
9
Anhydrobiosis Research Group, Division of Biomaterial Science, Institute of Agrobiological Sciences, National Agriculture and Food Research Organization, Tsukuba 305-8634, Japan
10
Department of Regulatory Transcriptomics for Medical Genetic Diagnostics, Graduate Schoole of Medical Sciences, Juntendo University, Tokyo 113-8421, Japan
11
RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama 351-0198, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Yansheng Du
Biology 2021, 10(7), 607; https://doi.org/10.3390/biology10070607
Received: 26 March 2021
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Revised: 21 June 2021
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Accepted: 24 June 2021
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Published: 30 June 2021
Simple Summary
We found that incubation with a solution containing ~50 mM neodymium (one of the rare-earth elements, REE) induces a rapid of active metabolism in mammalian cells. We have named this state REEbernation and found that the process involves a rapid replacement of calcium with neodymium in membranes and organelles of a cell, allowing it to maintain its shape and membrane integrity under extreme conditions, including vacuum. Furthermore, phosphate exchange is blocked because of non-dissolvable neodymium salts formation, which “discharged” the cell. We also showed that REEbernation is characterized by instant shutting down RNA transcriptional activity in the cells, providing an intriguing opportunity to study a snapshot of gene expression at a given time point. Finally, we found that the REEbernation state is reversible, and we could restore the metabolism and proliferation capacity of the cells. The REEbernation provides a new method to reversibly place a cell into “on-hold” mode, opening opportunities to develop protocols for biological samples fixation with a minimum effect on the omics profile for biomedical needs.
Until now, the ability to reversibly halt cellular processes has been limited to cryopreservation and several forms of anabiosis observed in living organisms. In this paper we show that incubation of living cells with a solution containing ~50 mM neodymium induces a rapid shutdown of intracellular organelle movement and all other evidence of active metabolism. We have named this state REEbernation (derived from the terms REE (rare earth elements) and hibernation) and found that the process involves a rapid replacement of calcium with neodymium in membranes and organelles of a cell, allowing it to maintain its shape and membrane integrity under extreme conditions, such as low pressure. Furthermore, phosphate exchange is blocked as a result of non-dissolvable neodymium salts formation, which “discharged” the cell. We further showed that REEbernation is characterized by an immediate cessation of transcriptional activity in observed cells, providing an intriguing opportunity to study a snapshot of gene expression at a given time point. Finally, we found that the REEbernation state is reversible, and we could restore the metabolism and proliferation capacity of the cells. The REEbernation, in addition to being an attractive model to further investigate the basic mechanisms of cell metabolism control, also provides a new method to reversibly place a cell into “on-hold” mode, opening opportunities to develop protocols for biological samples fixation with a minimum effect on the omics profile for biomedical needs.
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Keywords:
cells metabolism; anabiosis; ametabolic state
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MDPI and ACS Style
Subbot, A.; Kondratieva, S.; Novikov, I.; Gogoleva, N.; Kozlova, O.; Chebotar, I.; Gazizova, G.; Ryabova, A.; Vorontsova, M.; Kikawada, T.; Shagimardanova, E.; Gusev, O. Life-On-Hold: Lanthanoids Rapidly Induce a Reversible Ametabolic State in Mammalian Cells. Biology 2021, 10, 607. https://doi.org/10.3390/biology10070607
AMA Style
Subbot A, Kondratieva S, Novikov I, Gogoleva N, Kozlova O, Chebotar I, Gazizova G, Ryabova A, Vorontsova M, Kikawada T, Shagimardanova E, Gusev O. Life-On-Hold: Lanthanoids Rapidly Induce a Reversible Ametabolic State in Mammalian Cells. Biology. 2021; 10(7):607. https://doi.org/10.3390/biology10070607
Chicago/Turabian StyleSubbot, Anastasia, Sabina Kondratieva, Ivan Novikov, Natalia Gogoleva, Olga Kozlova, Igor Chebotar, Guzel Gazizova, Anastasia Ryabova, Maria Vorontsova, Takahiro Kikawada, Elena Shagimardanova, and Oleg Gusev. 2021. "Life-On-Hold: Lanthanoids Rapidly Induce a Reversible Ametabolic State in Mammalian Cells" Biology 10, no. 7: 607. https://doi.org/10.3390/biology10070607
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