Bio-Engineering
22 Mar 2021

Mitochondrial processes within cells sourced from hibernators and non-hibernators in altered gravity

Understanding the mechanisms and eventually inducing hibernation in humans could potentially revolutionize deep space travel and medicine [1]. Hibernation is shown to have reduced exposure to radiation effects, greatly reduces metabolism and energy consumption [2-4]. Hibernation could also bypass the psychological issues of long-term space travel. ESA has engaged in studies to assess and increase the understanding of hibernation, its underlying mechanisms as well as potential opportunities for human spaceflight since 2004, assisted by an active Topical Team [5-7].

In the proposed series of experiments in this study, we seek to study if and how metabolic pathways and mitochondrial activity are affected by conditions of altered gravity (hyper or hypo) in the context of hibernation/torpor. The metabolism of cells has been widely studied in such conditions in the context of physiology and disease pathology during space exploration. For instance, a study by Michaletti et al., demonstrated the dysregulation of mitochondrial homeostasis, as well as a reduction in the formation of mitochondrial proteins in primary human osteoblasts during periods of gravitational unloading [8]. In this scenario, it was also noted that the efficiencies of the electron transport chain processes were significantly reduced.

While this work was carried out in the context of long-term bone health of astronauts, a similar study found that conditions of microgravity induced autophagy in Hodgkin’s lymphoma cells [9]. In this study, it was noted that there was an increase in ROS (reactive oxygen species) production, and a decrease in mitochondrial function (decreased ATP synthase, ATP and mitochondrial mass). Furthermore, simulated microgravity has also been shown to induce mitochondrial dysfunction in rat arteries, suggesting a trend towards cardiovascular deconditioning and cerebral oxidative injury [10].

Project overview

In this study, we aim to study mitochondrial behaviour in cells with a focus on the effect of altered gravity and corresponding metabolic changes. We seek to use cells sourced from hibernating animals and non-hibernating animals to study mitochondrial behaviour under conditions of hypergravity. While the preferred source of cells would be the ground squirrel, cells from other animals could be sourced if advantageous. This study could inspire solutions to challenges facing human physiology under conditions of altered gravity and could potentially provide insights towards understanding developmental biology of hibernator sourced cells in extreme conditions. An alternative route to this study could also be taken to understand the mechanobiological impact of the cell-types in altered gravity and if there exist significant differences.


References

  1. A. Michaletti, M. Gioia, U. Tarantino, and L. Zolla, “Effects of microgravity on osteoblast mitochondria: A proteomic and metabolomics profile,” Sci. Rep., vol. 7, no. 1, Dec. 2017, doi: 10.1038/s41598-017-15612-1.
  2. W. A. Da Silveira et al., “Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact,” Cell, vol. 183, pp. 1185-1201.e20, 2020, doi: 10.1016/j.cell.2020.11.002.
  3. J. Ou et al., “iPSCs from a Hibernator Provide a Platform for Studying Cold Adaptation and Its Potential Medical Applications,” Cell, vol. 173, no. 4, pp. 851-863.e16, May 2018, doi: 10.1016/j.cell.2018.03.010.
  4. A. Choukèr, J. Bereiter-Hahn, D. Singer, and G. Heldmaier, “Hibernating astronauts—science or fiction?,” Pflugers Archiv European Journal of Physiology, vol. 471, no. 6. Springer Verlag, pp. 819–828, Jun. 01, 2019, doi: 10.1007/s00424-018-2244-7.
  5. M. Cerri et al., “Hibernation for space travel: Impact on radioprotection,” Life Sciences in Space Research, vol. 11. Elsevier Ltd, pp. 1–9, Nov. 01, 2016, doi: 10.1016/j.lssr.2016.09.001.
  6. T. Squire, A. Ryan, S. Bernard, and S. Bernard Radioprotective, “Radioprotective effects of induced astronaut torpor and advanced propulsion systems during deep space travel,” Life Sci. Sp. Res., vol. 26, 2020, doi: 10.1016/j.lssr.2020.05.005ï.
  7. W. Tinganelli et al., “Molecular Sciences Hibernation and Radioprotection: Gene Expression in the Liver and Testicle of Rats Irradiated under Synthetic Torpor,” Int. J. Mol. Sci, vol. 20, p. 352, 2019, doi: 10.3390/ijms20020352.
  8. G. Heldmaier, S. Ortmann, and R. Elvert, “Natural hypometabolism during hibernation and daily torpor in mammals,” in Respiratory Physiology and Neurobiology, Aug. 2004, vol. 141, no. 3, pp. 317–329, doi: 10.1016/j.resp.2004.03.014.
  9. “Hibernation | ACT of ESA.” https://www.esa.int/gsp/ACT/projects/hibernation/ (accessed Mar. 19, 2021).
  10. G. Petit et al., “Hibernation and Torpor: Prospects for Human Spaceflight,” in Handbook of Life Support Systems for Spacecraft and Extraterrestrial Habitats, Springer International Publishing, 2018, pp. 1–15.
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Advanced Concepts Team