A conserved role of Parkinson-associated DJ-1 metabolites in sperm motility, mitosis, and embryonic development
A conserved role of Parkinson-associated DJ-1 metabolites in sperm motility, mitosis, and embryonic development
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.
Bour Susanne、P¨|rez-S¨￠nchez Horacio、Hyman Anthony A.、Stief Christian G.、Pan-Montojo Francisco、Poser Ina、Alba-Alejandre Irene、Falkai Peter、Kluge Christoph、Trottmann Matthias、Dening Yanina、Balbach Melanie、Naumann Ronald、Oertel Reinhard、den Haan Helena、Accardi Davide、Dieterich Marianne、B?ckmann Rainer A.、Ram¨arez-¨￠lvarez In¨|s
Department of Urology, University HospitalBioinformatics and High Performance Computing Research Group (BIO-HPC), Computer Engineering Department, Universidad Cat¨?lica de Murcia (UCAM)Max-Planck Institute for Cell Biology and GeneticsDepartment of Urology, University HospitalDepartment of Neurology, University Hospital||Department of Psychiatry, University Hospital||Munich Cluster for Systems Neurology (SyNergy)Max-Planck Institute for Cell Biology and GeneticsDepartment of Gynecology and Obstetrics, Ludwig-Maximilian University MunichDepartment of Psychiatry, University HospitalComputational Biology, Department of Biology, Friedrich-Alexander UniversityDepartment of Urology, University HospitalDepartment of Neurology, University Hospital||Department of Psychiatry, University HospitalDepartment of Pharmacology, Weill Cornell Medical CollegeMax-Planck Institute for Cell Biology and GeneticsInstitute of Clinical Pharmacology, Medical Faculty, Technical University Dresden Fiedlerstrasse 27Bioinformatics and High Performance Computing Research Group (BIO-HPC), Computer Engineering Department, Universidad Cat¨?lica de Murcia (UCAM)Max-Planck Institute for Cell Biology and GeneticsDepartment of Neurology, University Hospital||Munich Cluster for Systems Neurology (SyNergy)Computational Biology, Department of Biology, Friedrich-Alexander UniversityDepartment of Neurology, University Hospital||Munich Cluster for Systems Neurology (SyNergy)
基础医学生物化学生理学
Bour Susanne,P¨|rez-S¨￠nchez Horacio,Hyman Anthony A.,Stief Christian G.,Pan-Montojo Francisco,Poser Ina,Alba-Alejandre Irene,Falkai Peter,Kluge Christoph,Trottmann Matthias,Dening Yanina,Balbach Melanie,Naumann Ronald,Oertel Reinhard,den Haan Helena,Accardi Davide,Dieterich Marianne,B?ckmann Rainer A.,Ram¨arez-¨￠lvarez In¨|s.A conserved role of Parkinson-associated DJ-1 metabolites in sperm motility, mitosis, and embryonic development[EB/OL].(2025-03-28)[2025-05-12].https://www.biorxiv.org/content/10.1101/2021.01.16.426934.点此复制
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