Zhang Weilin, Siraj Sami, Zhang Rong, Chen Quan
a The State Key Laboratory of Membrane Biology , Institute of Zoology, Chinese Academy of Sciences , Beijing , China.
b Sino-Danish Center for Education and Research , Beijing , China.
Autophagy. 2017 Jun 3;13(6):1080-1081. doi: 10.1080/15548627.2017.1300224. Epub 2017 Mar 21.
Mitophagy plays pivotal roles in the selective disposal of unwanted mitochondria, and accumulation of damaged mitochondria has been linked to aging-related diseases. However, definitive proof that mitophagy regulates mitochondrial quality in vivo is lacking. It is also largely unclear whether damaged mitochondria are the cause or just the consequence of these diseases. We previously showed that FUNDC1 is a mitophagy receptor that interacts with LC3 to mediate mitophagy in response to hypoxia in cultured cells. We established Fundc1 knockout mouse models and used genetic and biochemical approaches, including a synthetic peptide that blocks the FUNDC1-LC3 interaction, to demonstrate that mitophagy regulates both mitochondrial quantity and quality in vivo in response to hypoxia or hypoxic conditions caused by ischemia-reperfusion (I/R) heart injury. We found that hypoxic mitophagy regulates platelet activities. Furthermore, we found that hypoxic preconditioning induces FUNDC1-dependent mitophagy in platelets and reduces I/R-induced heart injury, suggesting a new strategy to protect cardiac function and fight cardiovascular diseases.
线粒体自噬在选择性清除不需要的线粒体方面发挥着关键作用，而受损线粒体的积累与衰老相关疾病有关。然而，缺乏线粒体自噬在体内调节线粒体质量的确切证据。此外，受损线粒体究竟是这些疾病的原因还是仅仅是其结果，目前也 largely 不清楚。我们之前表明，FUNDC1 是一种线粒体自噬受体，在培养细胞中，它与 LC3 相互作用以介导对缺氧的线粒体自噬反应。我们建立了 Fundc1 基因敲除小鼠模型，并使用遗传和生化方法，包括一种阻断 FUNDC1-LC3 相互作用的合成肽，来证明线粒体自噬在体内可响应缺氧或由缺血再灌注（I/R）心脏损伤引起的缺氧状况来调节线粒体的数量和质量。我们发现缺氧诱导的线粒体自噬调节血小板活性。此外，我们发现缺氧预处理可诱导血小板中 FUNDC1 依赖性的线粒体自噬，并减轻 I/R 诱导的心脏损伤，这提示了一种保护心脏功能和对抗心血管疾病的新策略。
