Role of TERT in regulating mitochondrial oxidative stress in diseases

doi:10.16352/j.issn.1001-6325.2024.10.1436

Abstract

Abstract: Oxidative stress is the result of imbalance between the formation of reactive oxygen species (ROS) and antioxidant level. Mitochondria are important organelles regulating oxidative stress. Telomerase reverse transcriptase (TERT) not only in the nucleus to maintain telomerase activity and telomere length, but also reversibly transits to mitochondria. Improving the activity of oxidative respiratory chain of mitochondria to reduce the production of mitochondrial reactive oxygen species (mtROS) and to activate GSH system as well as autophagy pathway to promote the clearance of mtROS are all important to down-regulate the level of mtROS, which will alleviate oxidative stress and damage and keep the REDOX balance of cells and the normal function of the body.

Key words: telomerase reverse transcriptase(TERT), oxidative stress, reactive oxygen species, ferroptosis, autophagy

CLC Number:

References

[1]Rosen J, Jakobs P, Ale-Agha N, et al. Non-canonical functions of telomerase reverse transcriptase-impact on redox homeostasis[J]. Redox Biol, 2020, 34:101543. doi: 10.1016/j.redox.2020.101543.
[2]Saretzki G. The telomerase connection of the brain and its implications for neurodegenerative diseases[J]. Stem Cells, 2023, 41:233-241. doi: 10.1093/stmcls/sxac078.
[3]Zhang Y, Tian K, Wei W, et al. Translocation of telomerase reverse transcriptase coincided with ATP release in postnatal cochlear supporting cells[J]. Neural Regen Res, 2023, 19: 1119-1125. doi: 10.4103/1673-5374.382862.
[4]Zhang B, Pan C, Feng C,et al. Role of mitochondrial reactive oxygen species in homeostasis regulation[J]. Redox Rep, 2022, 27:45-52. doi:10.1080/13510002.2022.2046423.
[5]Shekhova E. Mitochondrial reactive oxygen species as major effectors of antimicrobial immunity[J]. PLoS Pathog, 2020, 16:e1008470. doi: 10.1371/journal.ppat.1008470.
[6]Jie MM, Chang X, Zeng S,et al. Diverse regulatory manners of human telomerase reverse transcriptase[J]. Cell Commun Signal, 2019, 17:63. doi: 10.1186/s12964-019-0372-0.
[7]Hu W, Guo Y, Wang X, et al. Angiotensin-(1-7) promotes mitochondrial translocation of human telomerase reverse transcriptase in HUVECs through the TOM20 complex[J]. Arch Biochem Biophys, 2022, 722:109218. doi: 10.1016/j.abb.2022.109218.
[8]Metcalfe NB, Olsson M. How telomere dynamics are influenced by the balance between mitochondrial efficiency, reactive oxygen species production and DNA damage[J]. Mol Ecol, 2022, 31:6040-6052.doi: 10.1111/mec.16150.
[9]Zheng Q, Huang J, Wang G. Mitochondria, telomeres and telomerase subunits[J]. Front Cell Dev Biol, 2019, 7:274. doi: 10.3389/fcell.2019.00274.
[10]Li S, Xin Q, Fang G, et al. Upregulation of mitochondrial telomerase reverse transcriptase mediates the preventive effect of physical exercise on pathological cardiac hypertrophy via improving mitochondrial function and inhibiting oxidative Stress [J]. Biochim Biophys Acta Mol Basis Dis, 2024, 1870: 166859. doi: 10.1016/j.bbadis.2023.166859.
[11]Ale-Agha N, Jakobs P, Goy C,et al. Mitochondrial telomerase reverse transcriptase protects from myocardial ischemia/reperfusion injury by improving complex Ⅰ composi-tion and function[J]. Circulation, 2021, 144:1876-1890. doi: 10.1161/CIRCULATIONAHA.120.051923.
[12]Torimoto K, Eguchi S. Mitochondrial telomerase reverse transcriptase, a target for cardiovascular disease[J]. Function (Oxf), 2022, 3:zqac047.doi: 10.1093/function/zqac047.
[13]Chatterjee S, Hofer T, Costa A, et al. Telomerase therapy attenuates cardiotoxic effects of doxorubicin[J]. Mol Ther, 2021, 29:1395-1410.doi: 10.1016/j.ymthe.2020.12.035.
[14]Saretzki G, Wan T. Telomerase in brain: the new kid on the block and its role in neurodegenerative diseases [J]. Biomedicines, 2021, 9: 490. doi: 10.3390/biomedicines9050490.
[15]Wang W, Chen C, Wang Q,et al. Electroacupuncture pretreatment preserves telomerase reverse transcriptase function and alleviates postoperative cognitive dysfunction by suppressing oxidative stress and neuroinflammation in aged mice[J]. CNS Neurosci Ther, 2024,30:e14373. doi: 10.1111/cns.14373.
[16]Marinaccio J, Micheli E, Udroiu I,et al. TERT extra-telomeric roles: antioxidant activity and mitochondrial protection[J]. Int J Mol Sci, 2023, 24:4450. doi: 10.3390/ijms24054450.
[17]Wang X, Guo Y, Cui T, et al. Telomerase reverse transcriptase restores pancreatic microcirculation profiles and attenuates endothelial dysfunction by inhibiting mitochondrial superoxide production: a potential target for acute pancreatitis therapy [J]. Biomed Pharmacother, 2023, 167: 115576. doi: 10.1016/j.biopha.2023.115576.
[18]Wang X, Cui T, Zhang T, et al. Angiotensin-(1-7) restores microcirculation profiles in acute pancreatitis: secret of telomerase reverse transcriptase[J]. Pancreas, 2022, 51:1047-1055. doi: 10.1097/MPA.0000000000002139.
[19]Shin WH, Chung KC. Human telomerase reverse transcriptase positively regulates mitophagy by inhibiting the processing and cytoplasmic release of mitochondrial PINK1[J]. Cell Death Dis, 2020, 11:425. doi: 10.1038/s41419-020-2641-7.
[20]Agarwal N, Rinaldetti S, Cheikh BB,et al. TRIM28 is a transcriptional activator of the mutant TERT promoter in human bladder cancer[J]. Proc Natl Acad Sci USA, 2021, 118:e2102423118.doi: 10.1073/pnas.2102423118.
[21]Li L, Zhang H, Chen B, et al. BaZiBuShen alleviates cognitive deficits and regulates Sirt6/NRF2/HO-1 and Sirt6/P53-PGC-1α-TERT signaling pathways in aging Mice [J]. J Ethnopharmacol, 2022, 282: 114653. doi: 10.1016/j.jep.2021.114653.
[22]Yilmaz S, Bedir E, Ballar Kirmizibayrak P. The role of cycloastragenol at the intersection of NRF2/ARE, telomerase, and proteasome activity [J]. Free Radic Biol Med, 2022, 188: 105-116. doi: 10.1016/j.freeradbiomed.2022.06.230.
[23]Niu B, Liao K, Zhou Y, et al. Application of glutathione depletion in cancer therapy: enhanced ROS-based therapy, ferroptosis, and chemotherapy[J]. Biomaterials, 2021, 277: 121110. doi: 10.1016/j.biomaterials.2021.
121110.
[24]Hu Q, Liu XM, Liu ZR, et al. Dexmedetomidine reduces enteric glial cell injury induced by intestinal ischaemia-reperfusion injury through mitochondrial localization of TERT [J]. J Cell Mol Med, 2022, 26:2594-2606. doi: 10.1111/jcmm.17261.
[25]Ding X, Nie Z, She Z, et al. The regulation of ROS- and BECN1-mediated autophagy by human telomerase reverse transcriptase in glioblastoma[J]. Oxid Med Cell Longev, 2021, 2021:6636510. doi: 10.1155/2021/6636510.