The role of Lon-mediated proteolysis in the dynamics of mitochondrial nucleic acid-protein complexes
The role of Lon-mediated proteolysis in the dynamics of mitochondrial nucleic acid-protein complexes
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DOI：
10.1038/s41598-017-00632-8
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发表时间：
2017-04-04
影响因子：
4.6
通讯作者：
Pevala, Vladimir
中科院分区：
文献类型：
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作者：
Kunova, Nina;Ondrovicova, Gabriela;Pevala, Vladimir
线粒体类核蛋白由几组不同的蛋白质组成，其中许多蛋白质参与基本的细胞过程，如线粒体基因组的复制、修复和转录。真核生物中，ATP依赖性蛋白酶Lon被发现在中央类核区域内，尽管目前对其在那里的作用知之甚少。除了与线粒体类核蛋白结合外，人Lon还特异性地与RNA相互作用。最近，Lon被证明可以调节TFAM，这是人类线粒体中最丰富的mtDNA结构因子。为了确定Lon是否也调节其他线粒体类核或核糖体相关蛋白，我们研究了酿酒酵母TFAM功能同源物Abf2、酵母mtDNA维持蛋白Mgm101和两种人类线粒体蛋白Twinkle解旋酶和核糖体大亚基蛋白MrpL32的体外消化谱。Mgm101的降解也在酵母线粒体中进行了体内验证。这些实验表明，所有四种蛋白质都被Lon主动降解，但其中三种蛋白质在与核酸结合时受到保护，而Twinkle解旋酶则没有。这种调节机制可能促进线粒体类核的动态变化，这对于进行线粒体功能和维持线粒体稳态至关重要。
Mitochondrial nucleoids consist of several different groups of proteins, many of which are involved in essential cellular processes such as the replication, repair and transcription of the mitochondrial genome. The eukaryotic, ATP-dependent protease Lon is found within the central nucleoid region, though little is presently known about its role there. Aside from its association with mitochondrial nucleoids, human Lon also specifically interacts with RNA. Recently, Lon was shown to regulate TFAM, the most abundant mtDNA structural factor in human mitochondria. To determine whether Lon also regulates other mitochondrial nucleoid-or ribosome-associated proteins, we examined the in vitro digestion profiles of the Saccharomyces cerevisiae TFAM functional homologue Abf2, the yeast mtDNA maintenance protein Mgm101, and two human mitochondrial proteins, Twinkle helicase and the large ribosomal subunit protein MrpL32. Degradation of Mgm101 was also verified in vivo in yeast mitochondria. These experiments revealed that all four proteins are actively degraded by Lon, but that three of them are protected from it when bound to a nucleic acid; the Twinkle helicase is not. Such a regulatory mechanism might facilitate dynamic changes to the mitochondrial nucleoid, which are crucial for conducting mitochondrial functions and maintaining mitochondrial homeostasis.