Non-canonical functions of telomerase in oxidative defense
An increasing body of evidence indicates that non-canonical telomerase functions participate in a variety of biological pathways related to DNA repair and stress resistance. In addition to the regulation of cell growth and the cell cycle, the induction of apoptosis, or changes in global patterns of gene expression or chromatin status, telomerase and telomeres are involved in protecting cells against oxidative stress (Saretzki 2009; Ségal-Bendirdjian et al. 2019; Zheng et al. 2019). The impact of telomere biology in regard to cell functions under oxidative stress is documented by the crosstalk between telomeres/telomerase and mitochondria. It was determined that mitochondrial dysfunctions accelerate telomere shortening, thus indicating that mitochondrial ROS may act as a determinant of telomere-dependent senescence (Liu et al. 2002; Passos et al. 2007) and that telomere shortage and dysfunction can lead to the reprogramming of mitochondrial biosynthesis and alterations in mitochondrial functioning (Guo et al. 2011; Sahin et al. 2011). Additionally, it has been reported that in response to oxidative stress induced by hyperoxia, 80-90% of TERT (the catalytic subunit of telomerase) is transported from the nucleus into the mitochondria, ultimately resulting in a dramatic acceleration of telomere shortening. When the cellular conditions are shifted from hyperoxia back to normoxia, TERT is re-transported back to the nucleus, and telomere length is restored (Santos et al. 2006; Ahmed et al. 2008; Saretzki 2009). Telomerase may also exert a protective effect on mitochondrial functions. Under oxidative stress, it binds to mitochondrial DNA, increases respiratory chain activity, and protects against oxidative stress-induced damage (Haendeler et al. 2009). Finally, different tissues of the bank vole Myodes glareolus from the Chernobyl Exclusion Zone displayed reduced telomere length but upregulated telomerase activity. The upregulation of telomerase, in this case, appears to be associated with functions other than telomere maintenance, perhaps protection against a stressful environment (Kesäniemi et al. 2019).