Muscle denervation reduces mitochondrial biogenesis and mitochondrial translation factor expression in mice
Muscle denervation reduces mitochondrial biogenesis and mitochondrial translation factor expression in mice
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肌肉去神经减少小鼠线粒体生物发生和线粒体翻译因子表达
DOI：
10.1016/j.bbrc.2020.04.062
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发表时间：
2020
影响因子：
3.1
通讯作者：
Fujita Satoshi
中科院分区：
文献类型：
--
作者：
Yokokawa Takumi;Mori Risako;Suga Tadashi;Isaka Tadao;Hayashi Tatsuya;Fujita Satoshi
线粒体翻译过程，即线粒体DNA(MtDNA)编码的基因被翻译成相应的蛋白质，对线粒体的功能、生物发生和完整性至关重要。这一过程分为启动、延长、终止和有丝分裂体回收四个阶段，受特定翻译因子的调控，包括线粒体起始因子2和3(mtIF2和mtIF3)，线粒体延长因子Tu、ts和G1(mtEFTu、mtEFTs和mtEFG1)，线粒体翻译释放因子1样(MtRF1L)，以及线粒体回收因子1和2(mtRRF1和mtRRF2)。肌肉失神经降低了线粒体的生物量，导致骨骼肌萎缩。然而，目前尚不清楚去神经支配是否影响骨骼肌中线粒体翻译因子的表达。在这项研究中，我们假设去神经减少线粒体翻译因子的表达。因此，我们研究了肌肉失神经对比目鱼肌术后线粒体蛋白和线粒体翻译因子表达的影响。失神经支配导致比目鱼肌萎缩，激活了比目鱼肌泛素-蛋白酶体途径。此外，肌肉失神经减少了比目鱼肌中线粒体翻译因子以及核DNA和mtDNA编码的线粒体蛋白的表达。此外，在失神经后3天和7天，线粒体翻译因子的表达与mtDNA编码蛋白之间存在相关性。综上所述，这些结果表明，去神经支配导致的线粒体生物合成减少与小鼠骨骼肌线粒体翻译因子的变化相对应，为从分子水平上了解肌肉去神经支配对线粒体翻译过程的影响提供了新的视角。
The mitochondrial translation process, in which mitochondrial DNA (mtDNA)-encoded genes are translated into their corresponding proteins, is crucial for mitochondrial function, biogenesis, and integrity. This process is divided into four phases—initiation, elongation, termination, and mitoribosome recycling—which are regulated by specific translation factors, including mitochondrial initiation factor 2 and 3 (mtIF2 and mtIF3), mitochondrial elongation factor Tu, Ts, and G1 (mtEFTu, mtEFTs, and mtEFG1), mitochondrial translational release factor 1-like (mtRF1L), and mitochondrial recycling factor 1 and 2 (mtRRF1 and mtRRF2). Muscle denervation downregulates mitochondrial biomass and induces skeletal muscle atrophy. However, it is unknown whether denervation affects the expression of mitochondrial translation factors in skeletal muscle. In this study, we hypothesized that denervation decreases the expression of mitochondrial translation factors. Therefore, we investigated the effect of muscle denervation on mitochondrial protein and mitochondrial translation factor expression in soleus muscle after surgery. Denervation induced muscle atrophy and activated the ubiquitin-proteasome pathway in soleus muscle. Additionally, muscle denervation decreased the expression of mitochondrial translation factors as well as nuclear DNA and mtDNA-encoded mitochondrial proteins in soleus muscle. Further, a correlation was found between the expression of mitochondrial translation factors and mtDNA-encoded proteins three and seven days after denervation. Taken together, these results demonstrated that the denervation-induced decrease in mitochondrial biogenesis corresponded with changes in mitochondrial translation factors in murine skeletal muscle, providing novel molecular-level insight into the effects of muscle denervation on the mitochondrial translation process.