Naked mole rat TRF1 safeguards glycolytic capacity and telomere replication under low oxygen
- Others:
- Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire = Insitute of Interdisciplinary Research [Bruxelles, Belgique] (IRIBHM) ; Faculté de Médecine [Bruxelles] (ULB) ; Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)
- Brigham & Women's Hospital [Boston] (BWH) ; Harvard Medical School [Boston] (HMS)
- Institut de Recherche sur le Cancer et le Vieillissement (IRCAN) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
- University of Rochester [USA]
Description
The naked mole rat (NMR), a long-lived and cancer-resistant rodent, is highly resistant to hypoxia. Here, using robust cellular models wherein the mouse telomeric protein TRF1 is substituted by NMR TRF1 or its mutant forms, we show that TRF1 supports maximal glycolytic capacity under low oxygen, shows increased nuclear localization and association with telomeres, and protects telomeres from replicative stress. We pinpoint this evolutionary gain of metabolic function to specific amino acid changes in the homodimerization domain of this protein. We further find that NMR TRF1 accelerates telomere shortening. These findings reveal an evolutionary strategy to adapt telomere biology for metabolic control under an extreme environment.
Abstract
International audience
Additional details
- URL
- https://hal.archives-ouvertes.fr/hal-03510982
- URN
- urn:oai:HAL:hal-03510982v1
- Origin repository
- UNICA