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A conserved role of Parkinson-associated DJ-1 metabolites in sperm motility, mitosis, and embryonic development

Susanne Bour, Yanina Dening, View ORCID ProfileMelanie Balbach, View ORCID ProfileIna Poser, Inés Ramírez-Álvarez, View ORCID ProfileHelena den Haan, Christoph Kluge, Ronald Naumann, Reinhard Oertel, Irene Alba-Alejandre, Davide Accardi, View ORCID ProfileChristian G. Stief, View ORCID ProfileMarianne Dieterich, View ORCID ProfilePeter Falkai, View ORCID ProfileRainer A. Böckmann, Horacio Pérez-Sánchez, Anthony A. Hyman, View ORCID ProfileMatthias Trottmann, View ORCID ProfileFrancisco Pan-Montojo
doi: https://doi.org/10.1101/2021.01.16.426934
Susanne Bour
1Department of Urology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich
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Yanina Dening
2Department of Neurology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich
3Department of Psychiatry, University Hospital, LMU Munich, Nußbaumstr. 7, 80336 Munich
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Melanie Balbach
4Department of Pharmacology, Weill Cornell Medical College, New York City, NY
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  • ORCID record for Melanie Balbach
Ina Poser
5Max-Planck Institute for Cell Biology and Genetics, Pfotenhauerstr. 108, 01307 Dresden
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Inés Ramírez-Álvarez
2Department of Neurology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich
10Munich Cluster for Systems Neurology (SyNergy)
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Helena den Haan
6Bioinformatics and High Performance Computing Research Group (BIO-HPC), Computer Engineering Department, Universidad Católica de Murcia (UCAM), 30107 Murcia, Spain
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Christoph Kluge
7Computational Biology, Department of Biology, Friedrich-Alexander University, Staudtstr. 5, 91058 Erlangen
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Ronald Naumann
5Max-Planck Institute for Cell Biology and Genetics, Pfotenhauerstr. 108, 01307 Dresden
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Reinhard Oertel
8Institute of Clinical Pharmacology, Medical Faculty, Technical University Dresden Fiedlerstrasse 27, 01307 Dresden Germany
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Irene Alba-Alejandre
9Department of Gynecology and Obstetrics, Ludwig-Maximilian University Munich, Maistr. 11, 80337 Munich
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Davide Accardi
5Max-Planck Institute for Cell Biology and Genetics, Pfotenhauerstr. 108, 01307 Dresden
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Christian G. Stief
1Department of Urology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich
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Marianne Dieterich
2Department of Neurology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich
10Munich Cluster for Systems Neurology (SyNergy)
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Peter Falkai
3Department of Psychiatry, University Hospital, LMU Munich, Nußbaumstr. 7, 80336 Munich
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Rainer A. Böckmann
7Computational Biology, Department of Biology, Friedrich-Alexander University, Staudtstr. 5, 91058 Erlangen
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Horacio Pérez-Sánchez
6Bioinformatics and High Performance Computing Research Group (BIO-HPC), Computer Engineering Department, Universidad Católica de Murcia (UCAM), 30107 Murcia, Spain
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Anthony A. Hyman
5Max-Planck Institute for Cell Biology and Genetics, Pfotenhauerstr. 108, 01307 Dresden
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Matthias Trottmann
1Department of Urology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich
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Francisco Pan-Montojo
2Department of Neurology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich
3Department of Psychiatry, University Hospital, LMU Munich, Nußbaumstr. 7, 80336 Munich
10Munich Cluster for Systems Neurology (SyNergy)
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  • For correspondence: francisco.pan-montojo@med.uni-muenchen.de
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Abstract

Fertility rates in the developing world have dramatically dropped in the last decades. This drop is likely due to a decline in sperm quality and women having children at older ages. Loss of function mutations in DJ-1, a Parkinson’s associated gene, are linked to alterations in multiple cellular processes such as mitochondrial activity, ROS production or sperm motility and lead to an early onset of Parkinson’s disease and male infertility in humans and other species. Glycolate (GA) and D-lactate (DL), products of DJ-1 glyoxalase activity, sustain mitochondrial function and protect against environmental aggressions. We, therefore, tested whether these substances could also have a rescue effect on these phenotypes. Here, we show that DJ-1 loss of function not only affects sperm motility but also leads to defects in mitosis and an age-dependent increase in the abortion rate. Remarkably, whereas DL was only able to rescue embryonic lethality in C. elegans, GA rescued these phenotypes in all model systems tested and even increased sperm motility in wild-type sperm. These positive effects seem to be mediated through an increase in NAD(P)H production and the regulation of intracellular calcium. These findings not only strongly suggest GA as a new therapeutic candidate to improve male and female fertility but also show its potential to treat diseases associated with a decline in mitochondrial function or to improve mitochondrial function in aging.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Grammatical corrections. Reformulation.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 17, 2021.
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A conserved role of Parkinson-associated DJ-1 metabolites in sperm motility, mitosis, and embryonic development
Susanne Bour, Yanina Dening, Melanie Balbach, Ina Poser, Inés Ramírez-Álvarez, Helena den Haan, Christoph Kluge, Ronald Naumann, Reinhard Oertel, Irene Alba-Alejandre, Davide Accardi, Christian G. Stief, Marianne Dieterich, Peter Falkai, Rainer A. Böckmann, Horacio Pérez-Sánchez, Anthony A. Hyman, Matthias Trottmann, Francisco Pan-Montojo
bioRxiv 2021.01.16.426934; doi: https://doi.org/10.1101/2021.01.16.426934
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A conserved role of Parkinson-associated DJ-1 metabolites in sperm motility, mitosis, and embryonic development
Susanne Bour, Yanina Dening, Melanie Balbach, Ina Poser, Inés Ramírez-Álvarez, Helena den Haan, Christoph Kluge, Ronald Naumann, Reinhard Oertel, Irene Alba-Alejandre, Davide Accardi, Christian G. Stief, Marianne Dieterich, Peter Falkai, Rainer A. Böckmann, Horacio Pérez-Sánchez, Anthony A. Hyman, Matthias Trottmann, Francisco Pan-Montojo
bioRxiv 2021.01.16.426934; doi: https://doi.org/10.1101/2021.01.16.426934

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