MITOCHONDRIAL LOCALIZATION OF TINF2 CONTROLS REACTIVE OXYGEN SPECIES (ROS) GENERATION

Dysfunction of shorten telomeres and stabilization of ARF tumor suppressors are most characteristic properties during a replicative senescence. In primary cells, telomeres are gradually shortened via the incomplete DNA replication and . Meanwhile, ARF tumor suppressors are controlled by post-transcriptional regulatory processes, notably mRNA turnover and translation. TINF2 (TRF1-Interacting Nuclear Factor 2), a central shelterin component linking between TRF1 and TRF2, connects TPP1/POT1 to TRF1/TRF2 and contributes to telomere length regulation. In previous reports, mitochondrial localization of TINF2 suggests a link between telomeric proteins and mitochondrial metabolic pathway. Here, we observed reduced HuR level and enhanced TINF2 level during replicative senescence. In addition, we found that HuR regulates TINF2 expression in mitochondria, and mitochondrial TINF2 plays a role in the mitochondrial ROS generation and the induction of dysfunctional telomeres during a replicative senescence Our results demonstrate that TINF2-mediated ROS generation are concomitant to stabilization of the ARF tumor suppressor under orchestration of HuR during a replicative senescence.