Abstract
Mitochondrial functions and telomere functions have mostly been studied independently. In recent years, it, however, has become clear that there are intimate links between mitochondria, telomeres, and telomerase subunits. Mitochondrial dysfunctions cause telomere attrition, while telomere damage leads to reprogramming of mitochondrial biosynthesis and mitochondrial dysfunctions, which has important implications in aging and diseases. In addition, evidence has accumulated that telomere-independent functions of telomerase also exist and that the protein component of telomerase TERT shuttles between the nucleus and mitochondria under oxidative stress. Our previously published data show that the RNA component of telomerase TERC is also imported into mitochondria, processed, and exported back to the cytosol. These data show a complex regulation network where telomeres, nuclear genome, and mitochondria are co-regulated by multi-localization and multi-function proteins and RNAs. This review summarizes the connections between mitochondria and telomeres, the mitochondrion-related functions of telomerase subunits, and how they play a role in crosstalk between mitochondria and the nucleus.
Highlights
The aging field has seen a dramatic expansion in the last three decades with the discovery that it is controlled, at least to some extent, by evolutionally conserved pathways (Kenyon et al, 1993)
In an attempt to understand the biological function of TERT in the cell, fibroblasts untransfected or stably expressing WT or mutant TERT [with mutations in the mitochondrial targeting sequence (MTS)] that is catalytically active in the nucleus and proficient in cellular immortalization, but unable to enter mitochondria were compared (Sharma et al, 2012; Green et al, 2019)
Overexpression of the mitochondrion-localized TERT, but not the nucleus-localized TERT, has a protective effect on nuclear DNA damage and apoptosis after H2O2 treatment (Singhapol et al, 2013). These results suggest that cancer cells use nuclear exclusion and mitochondrial targeting of TERT to protect themselves from nuclear DNA damage and apoptosis
Summary
Mitochondrial functions and telomere functions have mostly been studied independently. Evidence has accumulated that telomere-independent functions of telomerase exist and that the protein component of telomerase TERT shuttles between the nucleus and mitochondria under oxidative stress. Our previously published data show that the RNA component of telomerase TERC is imported into mitochondria, processed, and exported back to the cytosol. These data show a complex regulation network where telomeres, nuclear genome, and mitochondria are co-regulated by multi-localization and multi-function proteins and RNAs. This review summarizes the connections between mitochondria and telomeres, the mitochondrionrelated functions of telomerase subunits, and how they play a role in crosstalk between mitochondria and the nucleus
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