AMPK activation serves a critical role in mitochondria quality control via modulating mitophagy in the heart under chronic hypoxia

Zhang,Huagang; Liu,Bo; Li,Tianbo; Zhu,Yun; Luo,Guiping; Jiang,Yunhan; Tang,Fuqin; Jian,Zhao; Xiao,Yingbin

doi:10.3892/ijmm.2017.3213

AMPK activation serves a critical role in mitochondria quality control via modulating mitophagy in the heart under chronic hypoxia

Authors:
- Huagang Zhang
- Bo Liu
- Tianbo Li
- Yun Zhu
- Guiping Luo
- Yunhan Jiang
- Fuqin Tang
- Zhao Jian
- Yingbin Xiao
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Affiliations: Department of Cardiovascular Surgery, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, P.R. China
Published online on: October 26, 2017 https://doi.org/10.3892/ijmm.2017.3213
Pages: 69-76
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Mitochondrial biogenesis is one of the generally accepted regulatory mechanisms in the heart under chronic hypoxia. The precise quantity and quality control of mitochondria is critical for the survival and function of cardiomyocytes. Mitochondrial autophagy, also known as mitophagy, which selectively eliminates dysfunctional and unwanted mitochondria, is the most important type of mitochondrial quality control. However, the detailed molecular mechanisms of mitophagy in cardiomyocytes have been largely undefined. The present study investigated the role of adenosine 5'‑monophosphate‑activated protein kinase (AMPK) in mitophagy regulation in cardiomyocytes under chronic hypoxia. H9c2 cells were cultured under hypoxic conditions (1% O2) for different time periods. Mitochondrial biogenesis was confirmed and hypoxia was found to induce the collapse of mitochondrial membrane potential (ΛΨm) and increase the number of dysfunctional mitochondria. As expected, mitochondrial autophagy was increased significantly in cardiomyocytes exposed to hypoxic conditions for 48 h. AMPK was activated under hypoxia. Notably, when the activation of AMPK was enhanced by the AMPK agonist AICAR, mitochondrial autophagy was increased accordingly. By contrast, when AMPK activation was blocked, mitochondrial autophagy was decreased and cardiomyocyte apoptosis was increased. In conclusion, in the present study, mitophagy was activated and played a crucial role in cardioprotection under chronic hypoxia. AMPK was involved in mitophagy regulation, thereby providing a potential therapeutic target for heart diseases associated with chronic hypoxia.

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