Life-On-Hold: Lanthanoids Rapidly Induce a Reversible Ametabolic State in Mammalian Cells
Research Institute of Eye Diseases, 119021 Moscow, Russia
Institute of Fundamental Medicine and Biology, Kazan Federal University, 420111 Kazan, Russia
Prokhorov General Physics Institute of the Russian Academy of Sciences, 119991 Moscow, Russia
Kazan Science Centre, Kazan Institute of Biochemistry and Biophysics, Russian Academy of Sciences, 420111 Kazan, Russia
Laboratory of Molecular Microbiology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia
Institute for Regenerative Medicine, Lomonosov State University, 119991 Moscow, Russia
Endocrinology Research Center, 115478 Moscow, Russia
Laboratory of Orphan Diseases, Moscow Institute of Physics and Technology, 141701 Moscow, Russia
Anhydrobiosis Research Group, Division of Biomaterial Science, Institute of Agrobiological Sciences, National Agriculture and Food Research Organization, Tsukuba 305-8634, Japan
Department of Regulatory Transcriptomics for Medical Genetic Diagnostics, Graduate Schoole of Medical Sciences, Juntendo University, Tokyo 113-8421, Japan
RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama 351-0198, Japan
Author to whom correspondence should be addressed.
Academic Editor: Yansheng Du
Received: 26 March 2021 / Revised: 21 June 2021 / Accepted: 24 June 2021 / Published: 30 June 2021
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.