The MOTS-c K14Q polymorphism in the mtDNA is associated with muscle fiber composition and muscular performance

Hiroshi Kumagai, Toshiharu Natsume, Su Jeong Kim, Takuro Tobina, Eri Miyamoto-Mikami, Keisuke Shiose, Noriko Ichinoseki-Sekine, Ryo Kakigi, Takamasa Tsuzuki, Brendan Miller, Kelvin Yen, Haruka Murakami, Motohiko Miyachi, Hirofumi Zempo, Shohei Dobashi, Shuichi Machida, Hiroyuki Kobayashi, Hisashi Naito, Pinchas Cohen, Noriyuki Fuku*

*この研究の対応する著者

研究成果査読

抄録

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.

本文言語English
論文番号130048
ジャーナルBiochimica et Biophysica Acta - General Subjects
1866
2
DOI
出版ステータスPublished - 2022 2

ASJC Scopus subject areas

  • 生物理学
  • 生化学
  • 分子生物学

フィンガープリント

「The MOTS-c K14Q polymorphism in the mtDNA is associated with muscle fiber composition and muscular performance」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル