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HIF-1 signaling: an emerging mechanism for mitochondrial dynamics

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Abstract 

A growing emphasis has been paid to the function of mitochondria in tumors, neurodegenerative disorders (NDs), and cardiovascular diseases. Mitochondria are oxygen-sensitive organelles whose function depends on their structural basis. Mitochondrial dynamics are critical in regulating the structure. Mitochondrial dynamics include fission, fusion, motility, cristae remodeling, and mitophagy. These processes could alter mitochondrial morphology, number, as well as distribution, to regulate complicated cellular signaling processes like metabolism. Meanwhile, they also could modulate cell proliferation and apoptosis. The initiation and progression of several diseases, such as tumors, NDs, cardiovascular disease, were all interrelated with mitochondrial dynamics. HIF-1 is a nuclear protein presented as heterodimers, and its transcriptional activity is triggered by hypoxia. It plays an important role in numerous physiological processes including the development of cardiovascular system, immune system, and cartilage. Additionally, it could evoke compensatory responses in cells during hypoxia through upstream and downstream signaling networks. Moreover, the alteration of oxygen level is a pivotal factor to promote mitochondrial dynamics and HIF-1 activation. HIF-1α might be a promising target for modulating mitochondrial dynamics to develop therapeutic approaches for NDs, immunological diseases, and other related diseases. Here, we reviewed the research progress of mitochondrial dynamics and the potential regulatory mechanism of HIF-1 in mitochondrial dynamics.

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This work was supported by Natural Science Foundation of China (No. 82073511).

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  1. Beijing Institute of Radiation Medicine, Beijing, 100850, People’s Republic of China

    Yu Xin, Li Zhao & Ruiyun Peng

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Yu Xin wrote the manuscript. Li Zhao and Ruiyun Peng revised the manuscript. All the authors read and approved the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

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Key Points

Mitochondrial dynamics directly affected the condition of mitochondria and modulated cell proliferation and apoptosis. The initiation and progression of tumors, neurodegenerative disorders, and cardiovascular disease are largely interrelated with mitochondrial dynamics.

HIF-1 evokes the compensatory responses of cells to hypoxia through regulating target genes to cause physiological and pathological alterations.

Oxygen served as a hub for interactions between mitochondrial dynamics and HIF-1.

HIF-1 regulated mitochondrial dynamics not only via promoting proliferation of abnormal cells but also through protecting cells against damage.

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Xin, Y., Zhao, L. & Peng, R. HIF-1 signaling: an emerging mechanism for mitochondrial dynamics. J Physiol Biochem 79, 489–500 (2023). https://doi.org/10.1007/s13105-023-00966-0

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