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).