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MicroRNA-125b alleviates hydrogen-peroxide-induced abnormal mitochondrial dynamics in HT22 cells by inhibiting p53

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Abstract

Micro-RNA125b (miR-125b) and tumor protein p53 (p53) are involved in the regulation of mitochondrial dynamics; however, the mechanism of their possible interaction during oxidative stress remains unclear. In this study, we investigated the role and mechanism of miR-125b and p53 in oxidative stress-induced mitochondrial damage in immortalized mouse hippocampal HT22 cells. Following stimulation with H2O2, we observed downregulation of miR-125b expression, upregulation of p53 expression, mitochondria were damaged and increased cell death. Overexpression of miR-125b alleviated mitochondrial damage and inhibited p53 expression. Furthermore, confocal and electron microscopy showed that overexpression of p53 eliminated the protective effect of miR-125b on the mitochondria. Thus, miR-125b alleviates abnormal mitochondrial homeostasis in H2O2-treated HT22 cells by suppressing p53 expression. Our data reveal a new model by which miR-125b influences mitochondrial dynamics.

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Data availability

The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

miR-125b:

micro-RNA 125b

p53:

tumor protein p53

GAPDH:

glyceraldehyde 3-phosphate dehydrogenase

FIS1:

mitochondrial fission 1 protein

MFN2:

mitofusin-2

OPA1:

optic atrophy 1

H2O2 :

hydrogen peroxide

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Acknowledgements

We express our gratitude to the Central Laboratory of Xiangya Hospital for the use of experimental equipment.

Funding

This work was supported by the National Natural Science Foundation of China (grant numbers 81873956 and 81671960).

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Authors and Affiliations

  1. Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, People’s Republic of China, 410008

    Yan Huang, Songyun Deng, Yuhang Ai, Yunan Mo, Wenchao Li, Qianyi Peng, Li Huang & Lina Zhang

  2. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of China, 410008

    Yan Huang, Yuhang Ai & Lina Zhang

Authors
  1. Yan Huang
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  2. Songyun Deng
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  3. Yuhang Ai
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  4. Yunan Mo
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  5. Wenchao Li
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  6. Qianyi Peng
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  7. Li Huang
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  8. Lina Zhang
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Contributions

Lina Zhang, Yan Huang, and Yuhang Ai: Conceptualization, Design. Yan Huang, Songyun Deng, and Yunan Mo: Investigation. Wenchao Li and Qianyi Peng: Data curation, Formal analysis. Lina Zhang and Li Huang: Resources. Yan Huang: Writing- Original draft preparation. All authors: Writing- Reviewing and Editing.

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Correspondence to Lina Zhang.

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Huang, Y., Deng, S., Ai, Y. et al. MicroRNA-125b alleviates hydrogen-peroxide-induced abnormal mitochondrial dynamics in HT22 cells by inhibiting p53. Metab Brain Dis 36, 601–608 (2021). https://doi.org/10.1007/s11011-020-00666-4

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