Hypoxic mitophagy regulates mitochondrial quality and platelet activation and determines severity of I/R heart injury
- Chinese Academy of Sciences, China
- Peking University, China
- Shanghai Jiaotong University, China
Abstract
Mitochondrial dysfunction underlies many prevalent diseases including heart disease arising from acute ischemia/reperfusion (I/R) injury. Here, we demonstrate that mitophagy, which selectively removes damaged or unwanted mitochondria, regulated mitochondrial quality and quantity in vivo. Hypoxia induced extensive mitochondrial degradation in a FUNDC1-depenent manner in platelets, and this was blocked by in vivo administration of a cell-penetrating peptide encompassing the LIR motif of FUNDC1 only in wild-type mice. Genetic ablation of Fundc1 impaired mitochondrial quality and increased mitochondrial mass in platelets and rendered the platelets insensitive to hypoxia and the peptide. Moreover, hypoxic mitophagy in platelets protected the heart from worsening of I/R injury. This represents a new mechanism of the hypoxic preconditioning effect which reduces I/R injury. Our results demonstrate a critical role of mitophagy in mitochondrial quality control and platelet activation, and suggest that manipulation of mitophagy by hypoxia or pharmacological approaches may be a novel strategy for cardioprotection.
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Author details
Funding
National Natural Science Foundation of China (31271529)
- Quan Chen
National Natural Science Foundation of China (81130045)
- Quan Chen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the Institute of Zoology, Chinese Academy of Sciences. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#08-133) of the Institute of Zoology, Chinese Academy of Sciences. The protocol was approved by the Committee on the Ethics of Animal Experiments of the Institute of Zoology, Chinese Academy of Sciences (Permit Number:2014-31301130). All surgery was performed under sodium pentobarbital anesthesia, and every effort was made to minimize suffering.
Copyright
© 2016, Zhang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Hypoxic mitophagy regulates mitochondrial quality and platelet activation and determines severity of I/R heart injury
eLife 5:e21407.
https://doi.org/10.7554/eLife.21407
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