The riddle of TERT inside the mitochondria

Telomerase Reverse Transcriptase (TERT) is now recognized to have some extra-telomeric roles and to be able to localize inside the mitochondria. In a previous work, we showed that TERT has a protective function against oxidative stress and a role in preserving mitochondria functionality. To better understand the putative mechanism of action and the reason of TERT translocation into mitochondria, we transduced two osteosarcoma cell lines (U2OS and SaOS-2), normally lacking TERT expression, with HA-tagged TERT protein, obtaining TERT overexpressing cells. It is important to note that SaOS-2 cells, differently from U2OS, are normally characterized by the expression of the Telomerase RNA Component (TERC). We showed clearly and unambiguously the presence of TERT inside mitochondria independently from the presence of TERC, taking advantage of Western blot and electron microscopy. In SaOS-2 cells, TERC was found in mitochondria, but not in their matrix where TERT is localized, indicating that TERT function in the mitochondria is independent from its canonical TERC counterpart. Since it is known that in the nucleus TERT is involved in gene expression regulation of different pathways, we have hypothesized a similar function in the mitochondrion. Mitochondrial chromatin immunoprecipitation (mIP) showed the binding of TERT to several mtDNA sequences; hence, we decided to study the possible implication of this binding on mitochondrial DNA replication and transcription, by measuring mtDNA copy number, BrdU incorporation and mitochondrial mRNA levels. Furthermore, to shed lights on our results, it would be interesting to investigate a TERT broad involvement in mitochondrial biogenesis.