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Accumulation of TERT in mitochondria exerts two opposing effects on apoptosis
Telomerase reverse transcriptase (TERT) is a protein that catalyzes the reverse transcription of telomere elongation. TERT is also expected to play a non‐canonical role beyond telomere lengthening since it localizes not only in the nucleus but also in mitochondria, where telomeres do not exist. Seve...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10476567/ https://www.ncbi.nlm.nih.gov/pubmed/37525387 http://dx.doi.org/10.1002/2211-5463.13682 |
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author | Ebata, Hiroshi Shima, Tomohiro Iizuka, Ryo Uemura, Sotaro |
author_facet | Ebata, Hiroshi Shima, Tomohiro Iizuka, Ryo Uemura, Sotaro |
author_sort | Ebata, Hiroshi |
collection | PubMed |
description | Telomerase reverse transcriptase (TERT) is a protein that catalyzes the reverse transcription of telomere elongation. TERT is also expected to play a non‐canonical role beyond telomere lengthening since it localizes not only in the nucleus but also in mitochondria, where telomeres do not exist. Several studies have reported that mitochondrial TERT regulates apoptosis induced by oxidative stress. However, there is still some controversy as to whether mitochondrial TERT promotes or inhibits apoptosis, mainly due to the lack of information on changes in TERT distribution in individual cells over time. Here, we simultaneously detected apoptosis and TERT localization after oxidative stress in individual HeLa cells by live‐cell tracking. Single‐cell tracking revealed that the stress‐induced accumulation of TERT in mitochondria caused apoptosis, but that accumulation increased over time until cell death. The results suggest a new model in which mitochondrial TERT has two opposing effects at different stages of apoptosis: it predetermines apoptosis at the first stage of cell‐fate determination, but also delays apoptosis at the second stage. As such, our data support a model that integrates the two opposing hypotheses on mitochondrial TERT's effect on apoptosis. Furthermore, detailed statistical analysis of TERT mutations, which have been predicted to inhibit TERT transport to mitochondria, revealed that these mutations suppress apoptosis independent of mitochondrial localization of TERT. Together, these results imply that the non‐canonical functions of TERT affect a wide range of mitochondria‐dependent and mitochondria‐independent apoptosis pathways. |
format | Online Article Text |
id | pubmed-10476567 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-104765672023-09-05 Accumulation of TERT in mitochondria exerts two opposing effects on apoptosis Ebata, Hiroshi Shima, Tomohiro Iizuka, Ryo Uemura, Sotaro FEBS Open Bio Research Articles Telomerase reverse transcriptase (TERT) is a protein that catalyzes the reverse transcription of telomere elongation. TERT is also expected to play a non‐canonical role beyond telomere lengthening since it localizes not only in the nucleus but also in mitochondria, where telomeres do not exist. Several studies have reported that mitochondrial TERT regulates apoptosis induced by oxidative stress. However, there is still some controversy as to whether mitochondrial TERT promotes or inhibits apoptosis, mainly due to the lack of information on changes in TERT distribution in individual cells over time. Here, we simultaneously detected apoptosis and TERT localization after oxidative stress in individual HeLa cells by live‐cell tracking. Single‐cell tracking revealed that the stress‐induced accumulation of TERT in mitochondria caused apoptosis, but that accumulation increased over time until cell death. The results suggest a new model in which mitochondrial TERT has two opposing effects at different stages of apoptosis: it predetermines apoptosis at the first stage of cell‐fate determination, but also delays apoptosis at the second stage. As such, our data support a model that integrates the two opposing hypotheses on mitochondrial TERT's effect on apoptosis. Furthermore, detailed statistical analysis of TERT mutations, which have been predicted to inhibit TERT transport to mitochondria, revealed that these mutations suppress apoptosis independent of mitochondrial localization of TERT. Together, these results imply that the non‐canonical functions of TERT affect a wide range of mitochondria‐dependent and mitochondria‐independent apoptosis pathways. John Wiley and Sons Inc. 2023-08-08 /pmc/articles/PMC10476567/ /pubmed/37525387 http://dx.doi.org/10.1002/2211-5463.13682 Text en © 2023 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Ebata, Hiroshi Shima, Tomohiro Iizuka, Ryo Uemura, Sotaro Accumulation of TERT in mitochondria exerts two opposing effects on apoptosis |
title | Accumulation of TERT in mitochondria exerts two opposing effects on apoptosis |
title_full | Accumulation of TERT in mitochondria exerts two opposing effects on apoptosis |
title_fullStr | Accumulation of TERT in mitochondria exerts two opposing effects on apoptosis |
title_full_unstemmed | Accumulation of TERT in mitochondria exerts two opposing effects on apoptosis |
title_short | Accumulation of TERT in mitochondria exerts two opposing effects on apoptosis |
title_sort | accumulation of tert in mitochondria exerts two opposing effects on apoptosis |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10476567/ https://www.ncbi.nlm.nih.gov/pubmed/37525387 http://dx.doi.org/10.1002/2211-5463.13682 |
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