【摘 要】
：
Receptor-mediated mitophagy plays a fundamental role in selectively removing damaged or unwanted mitochondria.We have recently identified that FUNDC1 is a novel
【机 构】
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TheStateKeyLaboratoryofMembraneBiology,ChineseAcademyofSciences,Beijing100101,China
【出 处】
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The 7th International Symposium on Autophagy 2015(第七届自噬国际研讨会
论文部分内容阅读
Receptor-mediated mitophagy plays a fundamental role in selectively removing damaged or unwanted mitochondria.We have recently identified that FUNDC1 is a novel receptor of mitophagy (Liu et al., Nature Cell Biology, 2012) and have revealed that mitochondrial Src kinase is able to phosphorylated FUNDC1 for the regulation of mitophagy (Chen et al.,Molecular Cell, 2014).To understand the physiological functions of FUNDC1 mediated mitophagy, we have obtained FUNDC1 conditional knockout mice and found that deficiency of FUNDC1 resulted in the dysfunction of platelets in blood.Our data showed that FUNDC1 is essential for mitophagy in platelets in vivo in response to hypoxia and mitochondrial membrane potiential uncouplers such as FCCP treatment, which promoted the interaction of FUNDC1 with LC3.FUNDC1 deficiency resulted in the impaired mitochondrial quality as revealed by the reduction of oxygen consumption rate, reduced ATP production and increased levels of mitochondrial ROS.FUNDC1 deficient mice have impaired platelet activation in response to ADP.A membrane-permeable peptide mimicing the unphosphorylated LIR domain of FUNDC1 effectively and significantly prevented interaction of FUNDC1 with LC3, and mitophagy, rescued the dysfunction of mitochondria and platelet activation.Our work will provide evidence to suggest a critical role of receptor mediated mitophagy in physiological setting and how mitochondrial quality contributes to the platelet activation.
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