RT Journal Article
SR Electronic
T1 A conserved role of Parkinson-associated DJ-1 metabolites in sperm motility, mitosis, and embryonic development
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.16.426934
DO 10.1101/2021.01.16.426934
A1 Susanne Bour
A1 Yanina Dening
A1 Melanie Balbach
A1 Ina Poser
A1 Inés Ramírez-Álvarez
A1 Helena den Haan
A1 Christoph Kluge
A1 Ronald Naumann
A1 Reinhard Oertel
A1 Irene Alba-Alejandre
A1 Davide Accardi
A1 Christian G. Stief
A1 Marianne Dieterich
A1 Peter Falkai
A1 Rainer A. Böckmann
A1 Horacio Pérez-Sánchez
A1 Anthony A. Hyman
A1 Matthias Trottmann
A1 Francisco Pan-Montojo
YR 2021
UL http://biorxiv.org/content/early/2021/01/17/2021.01.16.426934.1.abstract
AB 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 StatementThe authors have declared no competing interest.