The neuroprotective steroid progesterone promotes mitochondrial uncoupling, reduces cytosolic calcium and augments stress resistance in yeast cells

Authors:

Slaven Stekovic1,*, Christoph Ruckenstuhl1,*, Philipp Royer1, Christof Winkler-Hermaden1, Didac Carmona-Gutierrez1, Kai-Uwe Fröhlich1, Guido Kroemer3-8, and Frank Madeo1,2
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Affiliations:

1 Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria.

2 BioTechMed Graz, Austria.

3 Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France.

4 INSERM, U1138, Paris, France.

5 Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

6 Cell Biology & Metabolomics Platforms, Gustave Roussy Comprehensive Cancer Center, Villejuif, France.

7 Pôle de Biologie, Hôpital Européen Georges Pompidou, AP‐HP, Paris, France.

8 Karolinska Institute, Department of Women’s and Children’s Health, Karolinska University Hospital, 17176 Stockholm, Sweden.

* These authors contributed equally.

Keywords: 

TBI, traumatic brain injury, cell protection, cell stress, cell death, neuroprotection, progesterone, mitochondrial uncoupling.

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Corresponding Author(s):

Frank Madeo, Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50; 8010 Graz, Austria frank.madeo@uni-graz.at Christoph Ruckenstuhl, Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50; 8010 Graz, Austria ru.ruckenstuhl@uni-graz.at

Conflict of interest statement:

The authors declare no conflict of interest.

Please cite this article as:

Slaven Stekovic, Christoph Ruckenstuhl, Philipp Royer, Christof Winkler-Hermaden, Didac Carmona-Gutierrez, Kai-Uwe Fröhlich, Guido Kroemer, and Frank Madeo (2017). The neuroprotective steroid progesterone promotes mitochondrial uncoupling, reduces cytosolic calcium and augments stress resistance in yeast cells. Microbial Cell 4(6):191-199. doi: 10.15698/mic2017.06.577

© 2017 Stekovic et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

Abstract:

The steroid hormone progesterone is not only a crucial sex hormone, but also serves as a neurosteroid, thus playing an important role in brain function. Epidemiological data suggest that progesterone improves the recovery of patients after traumatic brain injury. Brain injuries are often connected to elevated calcium spikes, reactive oxygen species (ROS) and programmed cell death affecting neurons. Here, we establish a yeast model to study progesterone-mediated cytoprotection. External supply of progesterone protected yeast cells from apoptosis-inducing stress stimuli and resulted in elevated mitochondrial oxygen uptake accompanied by a drop in ROS generation and ATP levels during chronological aging. In addition, cellular Ca2+ concentrations were reduced upon progesterone treatment, and this effect occurred independently of known Ca2+ transporters and mitochondrial respiration. All effects were also independent of Dap1, the yeast orthologue of the progesterone receptor. Altogether, our observations provide new insights into the cytoprotective effects of progesterone.

doi: 10.15698/mic2017.06.577
Volume 4, pp. 191 to 199, published 31/05/2017.

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