The MOTS-c K14Q polymorphism in the mtDNA is associated with muscle fiber composition and muscular performance.
The MOTS-c K14Q polymorphism in the mtDNA is associated with muscle fiber composition and muscular performance.
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DOI：
10.1016/j.bbagen.2021.130048
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Fuku N
中科院分区：
文献类型：
--
作者：
Kumagai H;Natsume T;Kim SJ;Tobina T;Miyamoto-Mikami E;Shiose K;Ichinoseki-Sekine N;Kakigi R;Tsuzuki T;Miller B;Yen K;Murakami H;Miyachi M;Zempo H;Dobashi S;Machida S;Kobayashi H;Naito H;Cohen P;Fuku N
人体骨骼肌纤维是异质性的，因为它的慢肌纤维和快肌纤维的多样性。在人类中，慢动纤维基因表达与MOTS-c相关，MOTS-c是一种线粒体衍生的肽，被认为是一种运动模拟物。在MOTS-c开放阅读框中，存在东亚特异性的m.1382A>C多态性（rs111033358），该多态性改变了MOTS-c的第14个氨基酸（即K14Q），这是MOTS-c的一个变体，生物活性较低。在这里，我们研究了引起MOTS-c K14Q的m.1382A>C多态性对骨骼肌纤维组成和物理性能的影响。对211名日本健康人（102名男性和109名女性）进行了肌球蛋白重链（MHC）亚型（MHC- i、MHC- iia和MHC- iix）作为肌纤维组成指标的评估。研究人员用等速测力仪测量了86名经常运动的日本年轻男性的肌肉力量。对721名日本运动员和873名种族匹配对照进行了m.1382A >c多态性的等位基因频率评估。采用TaqMan SNP基因分型法分析m.1382A>C多态性基因型。携带m.1382A>C等位基因的个体比携带a等位基因的个体表现出更高的MHC-IIx比例，MHC-IIx是快速抽搐纤维的指数。携带m.1382A>C等位基因的男性，其腿部屈伸的峰值扭矩明显更高。此外，C等位基因频率在短跑/力量运动员（6.5%）、对照组（5.1%）和耐力运动员（2.9%）中依次较高。此外，年轻雄性小鼠每周注射一次MOTS-c中和抗体，连续四周模拟m.1382A>C的C等位基因，并评估MHC-fast和MHC-slow的蛋白表达水平。注射MOTS-c中和抗体的小鼠MHC-fast的表达高于对照小鼠。这些结果表明，东亚特异性m.1382A>C多态性的C等位基因导致MOTS-c K14Q通过调节骨骼肌纤维组成来促进短跑/力量表现。
Human skeletal muscle fiber is heterogenous due to its diversity of slow- and fast-twitch fibers. In human, slow-twitched fiber gene expression is correlated to MOTS-c, a mitochondria-derived peptide that has been characterized as an exercise mimetic. Within the MOTS-c open reading frame, there is an East Asian-specific m.1382A>C polymorphism (rs111033358) that changes the 14th amino acid of MOTS-c (i.e., K14Q), a variant of MOTS-c that has less biological activity. Here, we examined the influence of the m.1382A>C polymorphism causing MOTS-c K14Q on skeletal muscle fiber composition and physical performance. The myosin heavy chain (MHC) isoforms (MHC-I, MHC-IIa, and MHC-IIx) as an indicator of muscle fiber composition were assessed in 211 Japanese healthy individuals (102 men and 109 women). Muscular strength was measured in 86 physically active young Japanese men by using an isokinetic dynamometer. The allele frequency of the m.1382A>C polymorphism was assessed in 721 Japanese athletes and 873 ethnicity-matched controls. The m.1382A>C polymorphism genotype was analyzed by TaqMan SNP Genotyping Assay. Individuals with the C allele of the m.1382A>C exhibited a higher proportion of MHC-IIx, an index of fast-twitched fiber, than the A allele carriers. Men with the C allele of m.1382A>C exhibited significantly higher peak torques of leg flexion and extension. Furthermore, the C allele frequency was higher in the order of sprint/power athletes (6.5%), controls (5.1%), and endurance athletes (2.9%). Additionally, young male mice were injected with the MOTS-c neutralizing antibody once a week for four weeks to mimic the C allele of the m.1382A>C and assessed for protein expression levels of MHC-fast and MHC-slow. Mice injected with MOTS-c neutralizing antibody showed a higher expression of MHC-fast than the control mice. These results suggest that the C allele of the East Asian-specific m.1382A>C polymorphism leads to the MOTS-c K14Q contributes to the sprint/power performance through regulating skeletal muscle fiber composition.
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DOI：
10.18632/aging.202529
发表时间：
2021-01-19
期刊：
Aging
影响因子：
--
作者：
Zempo H;Kim SJ;Fuku N;Nishida Y;Higaki Y;Wan J;Yen K;Miller B;Vicinanza R;Miyamoto-Mikami E;Kumagai H;Naito H;Xiao J;Mehta HH;Lee C;Hara M;Patel YM;Setiawan VW;Moore TM;Hevener AL;Sutoh Y;Shimizu A;Kojima K;Kinoshita K;Arai Y;Hirose N;Maeda S;Tanaka K;Cohen P
通讯作者：
Cohen P
影响因子：
15.9
作者：
LILLIOJA, S;YOUNG, AA;BOGARDUS, C
通讯作者：
BOGARDUS, C
DOI：
10.1111/j.1748-1716.1975.tb10038.x
发表时间：
1975-01-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
ESSEN, B;JANSSON, E;SALTIN, B
通讯作者：
SALTIN, B
影响因子：
4.8
作者：
Handschin, Christoph;Chin, Sherry;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
影响因子：
7.8
作者：
Fuku N;Pareja-Galeano H;Zempo H;Alis R;Arai Y;Lucia A;Hirose N
通讯作者：
Hirose N