Cozzolino, M.; Ergun, Y.; Ristori, E.; Garg, A.; Imamoglu, G.; Seli, E. Disruption of Mitochondrial Unfolded Protein Response Results in Telomere Shortening in Mouse Oocytes and Somatic Cells. Aging 2024, doi:10.18632/aging.205543.
Cozzolino, M.; Ergun, Y.; Ristori, E.; Garg, A.; Imamoglu, G.; Seli, E. Disruption of Mitochondrial Unfolded Protein Response Results in Telomere Shortening in Mouse Oocytes and Somatic Cells. Aging 2024, doi:10.18632/aging.205543.
Cozzolino, M.; Ergun, Y.; Ristori, E.; Garg, A.; Imamoglu, G.; Seli, E. Disruption of Mitochondrial Unfolded Protein Response Results in Telomere Shortening in Mouse Oocytes and Somatic Cells. Aging 2024, doi:10.18632/aging.205543.
Cozzolino, M.; Ergun, Y.; Ristori, E.; Garg, A.; Imamoglu, G.; Seli, E. Disruption of Mitochondrial Unfolded Protein Response Results in Telomere Shortening in Mouse Oocytes and Somatic Cells. Aging 2024, doi:10.18632/aging.205543.
Abstract
Caseinolytic peptidase P (CLPP) plays a central role in mitochondrial unfolded protein response (mtUPR) by promoting the breakdown of misfolded proteins and setting in motion a cascade of reactions to re-establish protein homeostasis. Global germline deletion of Clpp in mice results in female infertility and accelerated follicular depletion. Telomeres, on the other hand, are tandem repeats of 5’-TTAGGG-3’ sequences found at the ends of the chromosomes. Telomeres are essential for maintaining chromosome stability during somatic cell division and their shortening is associated with cellular senescence and aging. In this study, we asked whether the infertility and ovarian aging phenotype caused by global germline deletion of Clpp is associated with somatic aging, and tested telomere length in tissues of young and aging mice. We found that impaired mtUPR caused by the lack of CLPP is associated with accelerated telomere shortening in both oocytes and somatic cells of aging mice. In addition, expression of several genes that maintain telomere integrity were decreased, and double strand DNA breaks were increased in telomeric regions. Our results highlight how impaired mtUPR can affect telomere integrity and demonstrate a link between loss of mitochondrial protein hemostasis, infertility, and somatic aging.
Keywords
Telomere length; aging; Clpp; mitochondrial dysfunction; unfolded protein response
Subject
Biology and Life Sciences, Aging
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
