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Title: Hypoxic Mitophagy Regulates Mitochondrial Quality and Platelet Activation and Determines Severity of I/R Heart Injury
Author: Weilin Zhang He Ren Chunling Xu Chongzhuo Zhu Hao Wu Dong Liu Jun Wang Lei Liu Wei Li Qi Ma Lei Du Ming Zheng Chuanmao Zhang Junling Liu Quan Chen
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-dependent 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.
Corresponding author: Chen Quan
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PubYear: 2016
Volume: 5
Issue: DOI: 10.7554/eLife.21407
Journal: eLife
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URL: https://elifesciences.org/content/5/e21407