Lysine 63-linked Polyubiquitination Is Dispensable for Parkin-mediated Mitophagy*
Lysine 63-linked Polyubiquitination Is Dispensable for Parkin-mediated Mitophagy*
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DOI：
10.1074/jbc.c114.580944
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发表时间：
2014-10
期刊：
影响因子：
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通讯作者：
Kahori Shiba-Fukushima;T. Inoshita;N. Hattori;Y. Imai
中科院分区：
文献类型：
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作者：
Kahori Shiba-Fukushima;T. Inoshita;N. Hattori;Y. Imai
背景：线粒体中的lys -63连锁泛素化发生在PINK1/ parkin介导的线粒体自噬中，其重要作用已被提出。结果：抑制lys -63连接的泛素化不会调节PINK1/帕金森介导的线粒体自噬和果蝇线粒体表型。结论：lys -63连锁泛素化在PINK1-Parkin通路中不可或缺。意义：本研究首次在体外和体内报道了lys -63连接的泛素化在PINK1-Parkin通路中的生物学意义。PINK1/帕金森介导的线粒体自噬被认为确保了神经元和其他细胞的线粒体质量控制。当线粒体膜电位丧失时（ΔΨm）， lys -63连接的多泛素链以帕金森依赖的方式在线粒体外膜上积累。然而，lys -63连接的多泛素化在线粒体自噬过程中的生理意义尚不完全清楚。在这里，我们报道通过去除Ubc13活性来抑制lys -63连接的多泛素化本质上既不影响PINK1的激活也不影响去极化线粒体的降解。此外，Ubc13的失活并没有调节PINK1敲低果蝇的线粒体表型。我们的数据表明，去极化线粒体上lys -63连接的多泛素链的形成并不是曾经认为的PINK1-Parkin通路的关键因素。
Background: Lys-63-linked ubiquitination in mitochondria occurs in PINK1/Parkin-mediated mitophagy, and its important roles have been proposed. Results: The suppression of Lys-63-linked ubiquitination did not modulate PINK1/Parkin-mediated mitophagy and Drosophila mitochondrial phenotypes. Conclusion: Lys-63-linked ubiquitination is dispensable for PINK1-Parkin pathway. Significance: This is the first study to report the biological significance of Lys-63-linked ubiquitination in PINK1-Parkin pathway in vitro and in vivo. PINK1/Parkin-mediated mitophagy is thought to ensure mitochondrial quality control in neurons as well as other cells. Upon the loss of mitochondrial membrane potential (ΔΨm), Lys-63-linked polyubiquitin chains accumulate on the mitochondrial outer membrane in a Parkin-dependent manner. However, the physiological significance of Lys-63-linked polyubiquitination during mitophagy is not fully understood. Here, we report that the suppression of Lys-63-linked polyubiquitination through the removal of Ubc13 activity essentially affects neither PINK1 activation nor the degradation of depolarized mitochondria. Moreover, the inactivation of Ubc13 did not modulate the mitochondrial phenotypes of PINK1 knockdown Drosophila. Our data indicate that the formation of Lys-63-linked polyubiquitin chains on depolarized mitochondria is not a key factor for the PINK1-Parkin pathway as was once thought.