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Mitochondria: Endosymbiont bacteria DNA sequence as a target against cancer

As the energy factory for the cell, the mitochondrion, through its role of adenosine triphosphate production by oxidative phosphorylation, can be regarded as the guardian of well regulated cellular metabolism; the integrity of mitochondrial functions, however, is particularly vulnerable in cancer du...

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Autores principales: Nagase, Hiroki, Watanabe, Takayoshi, Koshikawa, Nobuko, Yamamoto, Seigi, Takenaga, Keizo, Lin, Jason
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645765/
https://www.ncbi.nlm.nih.gov/pubmed/34533888
http://dx.doi.org/10.1111/cas.15143
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author Nagase, Hiroki
Watanabe, Takayoshi
Koshikawa, Nobuko
Yamamoto, Seigi
Takenaga, Keizo
Lin, Jason
author_facet Nagase, Hiroki
Watanabe, Takayoshi
Koshikawa, Nobuko
Yamamoto, Seigi
Takenaga, Keizo
Lin, Jason
author_sort Nagase, Hiroki
collection PubMed
description As the energy factory for the cell, the mitochondrion, through its role of adenosine triphosphate production by oxidative phosphorylation, can be regarded as the guardian of well regulated cellular metabolism; the integrity of mitochondrial functions, however, is particularly vulnerable in cancer due to the lack of superstructures such as histone and lamina folds to protect the mitochondrial genome from unintended exposure, which consequently elevates risks of mutation. In cancer, mechanisms responsible for enforcing quality control surveillance for identifying and eliminating defective mitochondria are often poorly regulated, and certain uneliminated mitochondrial DNA (mtDNA) mutations and polymorphisms can be advantageous for the proliferation, progression, and metastasis of tumor cells. Such pathogenic mtDNA aberrations are likely to increase and occasionally be homoplasmic in cancer cells and, intriguingly, in normal cells in the proximity of tumor microenvironments as well. Distinct characteristics of these abnormalities in mtDNA may provide a new path for cancer therapy. Here we discuss a promising novel therapeutic strategy, using the sequence‐specific properties of pyrrole‐imidazole polyamide‐triphenylphosphonium conjugates, against cancer for clearing abnormal mtDNA by reactivating mitochondrial quality control surveillance.
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spelling pubmed-86457652021-12-17 Mitochondria: Endosymbiont bacteria DNA sequence as a target against cancer Nagase, Hiroki Watanabe, Takayoshi Koshikawa, Nobuko Yamamoto, Seigi Takenaga, Keizo Lin, Jason Cancer Sci Review Articles As the energy factory for the cell, the mitochondrion, through its role of adenosine triphosphate production by oxidative phosphorylation, can be regarded as the guardian of well regulated cellular metabolism; the integrity of mitochondrial functions, however, is particularly vulnerable in cancer due to the lack of superstructures such as histone and lamina folds to protect the mitochondrial genome from unintended exposure, which consequently elevates risks of mutation. In cancer, mechanisms responsible for enforcing quality control surveillance for identifying and eliminating defective mitochondria are often poorly regulated, and certain uneliminated mitochondrial DNA (mtDNA) mutations and polymorphisms can be advantageous for the proliferation, progression, and metastasis of tumor cells. Such pathogenic mtDNA aberrations are likely to increase and occasionally be homoplasmic in cancer cells and, intriguingly, in normal cells in the proximity of tumor microenvironments as well. Distinct characteristics of these abnormalities in mtDNA may provide a new path for cancer therapy. Here we discuss a promising novel therapeutic strategy, using the sequence‐specific properties of pyrrole‐imidazole polyamide‐triphenylphosphonium conjugates, against cancer for clearing abnormal mtDNA by reactivating mitochondrial quality control surveillance. John Wiley and Sons Inc. 2021-10-04 2021-12 /pmc/articles/PMC8645765/ /pubmed/34533888 http://dx.doi.org/10.1111/cas.15143 Text en © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Review Articles
Nagase, Hiroki
Watanabe, Takayoshi
Koshikawa, Nobuko
Yamamoto, Seigi
Takenaga, Keizo
Lin, Jason
Mitochondria: Endosymbiont bacteria DNA sequence as a target against cancer
title Mitochondria: Endosymbiont bacteria DNA sequence as a target against cancer
title_full Mitochondria: Endosymbiont bacteria DNA sequence as a target against cancer
title_fullStr Mitochondria: Endosymbiont bacteria DNA sequence as a target against cancer
title_full_unstemmed Mitochondria: Endosymbiont bacteria DNA sequence as a target against cancer
title_short Mitochondria: Endosymbiont bacteria DNA sequence as a target against cancer
title_sort mitochondria: endosymbiont bacteria dna sequence as a target against cancer
topic Review Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645765/
https://www.ncbi.nlm.nih.gov/pubmed/34533888
http://dx.doi.org/10.1111/cas.15143
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