The crosstalk between HIFs and mitochondrial dysfunctions in cancer development
Abstract Mitochondria are essential cellular organelles that are involved in regulating cellular energy, metabolism, survival, and proliferation. To some extent, cancer is a genetic and metabolic disease that is closely associated with mitochondrial dysfunction. Hypoxia-inducible factors (HIFs), whi...
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doaj-5c7f0ff96eec4255a2c9443b754a49752021-03-11T11:16:13ZengNature Publishing GroupCell Death and Disease2041-48892021-02-0112211310.1038/s41419-021-03505-1The crosstalk between HIFs and mitochondrial dysfunctions in cancer developmentXingting Bao0Jinhua Zhang1Guomin Huang2Junfang Yan3Caipeng Xu4Zhihui Dou5Chao Sun6Hong Zhang7Department of Medical Physics, Institute of Modern Physics, Chinese Academy of SciencesDepartment of Medical Physics, Institute of Modern Physics, Chinese Academy of SciencesDepartment of Medical Physics, Institute of Modern Physics, Chinese Academy of SciencesDepartment of Medical Physics, Institute of Modern Physics, Chinese Academy of SciencesDepartment of Medical Physics, Institute of Modern Physics, Chinese Academy of SciencesDepartment of Medical Physics, Institute of Modern Physics, Chinese Academy of SciencesDepartment of Medical Physics, Institute of Modern Physics, Chinese Academy of SciencesDepartment of Medical Physics, Institute of Modern Physics, Chinese Academy of SciencesAbstract Mitochondria are essential cellular organelles that are involved in regulating cellular energy, metabolism, survival, and proliferation. To some extent, cancer is a genetic and metabolic disease that is closely associated with mitochondrial dysfunction. Hypoxia-inducible factors (HIFs), which are major molecules that respond to hypoxia, play important roles in cancer development by participating in multiple processes, such as metabolism, proliferation, and angiogenesis. The Warburg phenomenon reflects a pseudo-hypoxic state that activates HIF-1α. In addition, a product of the Warburg effect, lactate, also induces HIF-1α. However, Warburg proposed that aerobic glycolysis occurs due to a defect in mitochondria. Moreover, both HIFs and mitochondrial dysfunction can lead to complex reprogramming of energy metabolism, including reduced mitochondrial oxidative metabolism, increased glucose uptake, and enhanced anaerobic glycolysis. Thus, there may be a connection between HIFs and mitochondrial dysfunction. In this review, we systematically discuss the crosstalk between HIFs and mitochondrial dysfunctions in cancer development. Above all, the stability and activity of HIFs are closely influenced by mitochondrial dysfunction related to tricarboxylic acid cycle, electron transport chain components, mitochondrial respiration, and mitochondrial-related proteins. Furthermore, activation of HIFs can lead to mitochondrial dysfunction by affecting multiple mitochondrial functions, including mitochondrial oxidative capacity, biogenesis, apoptosis, fission, and autophagy. In general, the regulation of tumorigenesis and development by HIFs and mitochondrial dysfunction are part of an extensive and cooperative network.https://doi.org/10.1038/s41419-021-03505-1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xingting Bao Jinhua Zhang Guomin Huang Junfang Yan Caipeng Xu Zhihui Dou Chao Sun Hong Zhang |
spellingShingle |
Xingting Bao Jinhua Zhang Guomin Huang Junfang Yan Caipeng Xu Zhihui Dou Chao Sun Hong Zhang The crosstalk between HIFs and mitochondrial dysfunctions in cancer development Cell Death and Disease |
author_facet |
Xingting Bao Jinhua Zhang Guomin Huang Junfang Yan Caipeng Xu Zhihui Dou Chao Sun Hong Zhang |
author_sort |
Xingting Bao |
title |
The crosstalk between HIFs and mitochondrial dysfunctions in cancer development |
title_short |
The crosstalk between HIFs and mitochondrial dysfunctions in cancer development |
title_full |
The crosstalk between HIFs and mitochondrial dysfunctions in cancer development |
title_fullStr |
The crosstalk between HIFs and mitochondrial dysfunctions in cancer development |
title_full_unstemmed |
The crosstalk between HIFs and mitochondrial dysfunctions in cancer development |
title_sort |
crosstalk between hifs and mitochondrial dysfunctions in cancer development |
publisher |
Nature Publishing Group |
series |
Cell Death and Disease |
issn |
2041-4889 |
publishDate |
2021-02-01 |
description |
Abstract Mitochondria are essential cellular organelles that are involved in regulating cellular energy, metabolism, survival, and proliferation. To some extent, cancer is a genetic and metabolic disease that is closely associated with mitochondrial dysfunction. Hypoxia-inducible factors (HIFs), which are major molecules that respond to hypoxia, play important roles in cancer development by participating in multiple processes, such as metabolism, proliferation, and angiogenesis. The Warburg phenomenon reflects a pseudo-hypoxic state that activates HIF-1α. In addition, a product of the Warburg effect, lactate, also induces HIF-1α. However, Warburg proposed that aerobic glycolysis occurs due to a defect in mitochondria. Moreover, both HIFs and mitochondrial dysfunction can lead to complex reprogramming of energy metabolism, including reduced mitochondrial oxidative metabolism, increased glucose uptake, and enhanced anaerobic glycolysis. Thus, there may be a connection between HIFs and mitochondrial dysfunction. In this review, we systematically discuss the crosstalk between HIFs and mitochondrial dysfunctions in cancer development. Above all, the stability and activity of HIFs are closely influenced by mitochondrial dysfunction related to tricarboxylic acid cycle, electron transport chain components, mitochondrial respiration, and mitochondrial-related proteins. Furthermore, activation of HIFs can lead to mitochondrial dysfunction by affecting multiple mitochondrial functions, including mitochondrial oxidative capacity, biogenesis, apoptosis, fission, and autophagy. In general, the regulation of tumorigenesis and development by HIFs and mitochondrial dysfunction are part of an extensive and cooperative network. |
url |
https://doi.org/10.1038/s41419-021-03505-1 |
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