Life-On-Hold: Lanthanoids Rapidly Induce a Reversible Ametabolic State in Mammalian Cells
Anastasia Subbot,
Sabina Kondratieva,
Ivan Novikov,
Natalia Gogoleva,
Olga Kozlova,
Igor Chebotar,
Guzel Gazizova,
Anastasia Ryabova,
Maria Vorontsova,
Takahiro Kikawada,
Elena Shagimardanova,
Oleg Gusev
Affiliations
Anastasia Subbot
Research Institute of Eye Diseases, 119021 Moscow, Russia
Sabina Kondratieva
Institute of Fundamental Medicine and Biology, Kazan Federal University, 420111 Kazan, Russia
Ivan Novikov
Research Institute of Eye Diseases, 119021 Moscow, Russia
Natalia Gogoleva
Kazan Science Centre, Kazan Institute of Biochemistry and Biophysics, Russian Academy of Sciences, 420111 Kazan, Russia
Olga Kozlova
Institute of Fundamental Medicine and Biology, Kazan Federal University, 420111 Kazan, Russia
Igor Chebotar
Laboratory of Molecular Microbiology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia
Guzel Gazizova
Institute of Fundamental Medicine and Biology, Kazan Federal University, 420111 Kazan, Russia
Anastasia Ryabova
Prokhorov General Physics Institute of the Russian Academy of Sciences, 119991 Moscow, Russia
Maria Vorontsova
Institute for Regenerative Medicine, Lomonosov State University, 119991 Moscow, Russia
Takahiro Kikawada
Anhydrobiosis Research Group, Division of Biomaterial Science, Institute of Agrobiological Sciences, National Agriculture and Food Research Organization, Tsukuba 305-8634, Japan
Elena Shagimardanova
Institute of Fundamental Medicine and Biology, Kazan Federal University, 420111 Kazan, Russia
Oleg Gusev
Institute of Fundamental Medicine and Biology, Kazan Federal University, 420111 Kazan, Russia
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.
