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Autophagy-Induced HDAC6 Activity During Hypoxia Regulates Mitochondrial Energy Metabolism Through the β-Catenin/COUP-TFII Axis in Hepatocellular Carcinoma Cells
Hypoxia is one of the main driving forces that results in poor outcomes and drug resistance in hepatocellular carcinoma (HCC). As the critical cellular oxygen sensor, mitochondria respond to hypoxic stress by sending retrograde signals to the nucleus that initiate adaptive metabolic responses and ma...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636061/ https://www.ncbi.nlm.nih.gov/pubmed/34868939 http://dx.doi.org/10.3389/fonc.2021.742460 |
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author | Yan, Xiaoyu Qu, Xianzhi Liu, Buhan Zhao, Yuanxin Xu, Long Yu, Sihang Wang, Jian Wang, Liying Su, Jing |
author_facet | Yan, Xiaoyu Qu, Xianzhi Liu, Buhan Zhao, Yuanxin Xu, Long Yu, Sihang Wang, Jian Wang, Liying Su, Jing |
author_sort | Yan, Xiaoyu |
collection | PubMed |
description | Hypoxia is one of the main driving forces that results in poor outcomes and drug resistance in hepatocellular carcinoma (HCC). As the critical cellular oxygen sensor, mitochondria respond to hypoxic stress by sending retrograde signals to the nucleus that initiate adaptive metabolic responses and maintain the survival of HCC cells. Increasing evidence suggested autophagy contributes to sustain mitochondrial metabolic and quality control. Understanding how mitochondria communicate with the nucleus and alter transcription may provide promising targets for HCC treatment. In this study, we found mitochondrial undergoes selective degradation by autophagy under hypoxia. Furthermore, autophagy-activated HDAC6 not only promoted the nuclear translocation of β-catenin but also increased the affinity of β-catenin to the transcription repressor chicken ovalbumin upstream promoter-transcription factor 2 (COUP-TF II), which suppressed mitochondrial oxidative phosphorylation-related genes transcription. Our data showed that autophagy served as a critical mediator of integrating mitochondrial energy metabolism and nuclear transcription. HDAC6 may be a potential target for reducing the survival of HCC cells by interrupting mitochondria-nucleus crosstalk. |
format | Online Article Text |
id | pubmed-8636061 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86360612021-12-02 Autophagy-Induced HDAC6 Activity During Hypoxia Regulates Mitochondrial Energy Metabolism Through the β-Catenin/COUP-TFII Axis in Hepatocellular Carcinoma Cells Yan, Xiaoyu Qu, Xianzhi Liu, Buhan Zhao, Yuanxin Xu, Long Yu, Sihang Wang, Jian Wang, Liying Su, Jing Front Oncol Oncology Hypoxia is one of the main driving forces that results in poor outcomes and drug resistance in hepatocellular carcinoma (HCC). As the critical cellular oxygen sensor, mitochondria respond to hypoxic stress by sending retrograde signals to the nucleus that initiate adaptive metabolic responses and maintain the survival of HCC cells. Increasing evidence suggested autophagy contributes to sustain mitochondrial metabolic and quality control. Understanding how mitochondria communicate with the nucleus and alter transcription may provide promising targets for HCC treatment. In this study, we found mitochondrial undergoes selective degradation by autophagy under hypoxia. Furthermore, autophagy-activated HDAC6 not only promoted the nuclear translocation of β-catenin but also increased the affinity of β-catenin to the transcription repressor chicken ovalbumin upstream promoter-transcription factor 2 (COUP-TF II), which suppressed mitochondrial oxidative phosphorylation-related genes transcription. Our data showed that autophagy served as a critical mediator of integrating mitochondrial energy metabolism and nuclear transcription. HDAC6 may be a potential target for reducing the survival of HCC cells by interrupting mitochondria-nucleus crosstalk. Frontiers Media S.A. 2021-11-11 /pmc/articles/PMC8636061/ /pubmed/34868939 http://dx.doi.org/10.3389/fonc.2021.742460 Text en Copyright © 2021 Yan, Qu, Liu, Zhao, Xu, Yu, Wang, Wang and Su https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Yan, Xiaoyu Qu, Xianzhi Liu, Buhan Zhao, Yuanxin Xu, Long Yu, Sihang Wang, Jian Wang, Liying Su, Jing Autophagy-Induced HDAC6 Activity During Hypoxia Regulates Mitochondrial Energy Metabolism Through the β-Catenin/COUP-TFII Axis in Hepatocellular Carcinoma Cells |
title | Autophagy-Induced HDAC6 Activity During Hypoxia Regulates Mitochondrial Energy Metabolism Through the β-Catenin/COUP-TFII Axis in Hepatocellular Carcinoma Cells |
title_full | Autophagy-Induced HDAC6 Activity During Hypoxia Regulates Mitochondrial Energy Metabolism Through the β-Catenin/COUP-TFII Axis in Hepatocellular Carcinoma Cells |
title_fullStr | Autophagy-Induced HDAC6 Activity During Hypoxia Regulates Mitochondrial Energy Metabolism Through the β-Catenin/COUP-TFII Axis in Hepatocellular Carcinoma Cells |
title_full_unstemmed | Autophagy-Induced HDAC6 Activity During Hypoxia Regulates Mitochondrial Energy Metabolism Through the β-Catenin/COUP-TFII Axis in Hepatocellular Carcinoma Cells |
title_short | Autophagy-Induced HDAC6 Activity During Hypoxia Regulates Mitochondrial Energy Metabolism Through the β-Catenin/COUP-TFII Axis in Hepatocellular Carcinoma Cells |
title_sort | autophagy-induced hdac6 activity during hypoxia regulates mitochondrial energy metabolism through the β-catenin/coup-tfii axis in hepatocellular carcinoma cells |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636061/ https://www.ncbi.nlm.nih.gov/pubmed/34868939 http://dx.doi.org/10.3389/fonc.2021.742460 |
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