2017A Stekovic Microbial Cell Advanced Pub

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 Ca 2+ concentrations were reduced upon progesterone treatment, and this effect occurred independently of known Ca 2+ 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. The neuroprotective steroid progesterone promotes mitochondrial uncoupling, reduces cytosolic calcium and augments stress resistance in yeast cells Slaven Stekovic 1, *, Christoph Ruckenstuhl 1,+, *, Phillip Royer 1 , Christof Winkler-Hermaden 1 , Didac CarmonaGutierrez 1 , Kai-Uwe Fröhlich 1 , Guido Kroemer 3-8 , and Frank Madeo 1,2,+ 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. * Corresponding Author: Frank Madeo, Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50; 8010 Graz, Austria; E-mail: [email protected] Christoph Ruckenstuhl, Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50; 8010 Graz, Austria; E-mail: [email protected]