TY - JOUR
T1 - The MOTS-c K14Q polymorphism in the mtDNA is associated with muscle fiber composition and muscular performance
AU - Kumagai, Hiroshi
AU - Natsume, Toshiharu
AU - Kim, Su Jeong
AU - Tobina, Takuro
AU - Miyamoto-Mikami, Eri
AU - Shiose, Keisuke
AU - Ichinoseki-Sekine, Noriko
AU - Kakigi, Ryo
AU - Tsuzuki, Takamasa
AU - Miller, Brendan
AU - Yen, Kelvin
AU - Murakami, Haruka
AU - Miyachi, Motohiko
AU - Zempo, Hirofumi
AU - Dobashi, Shohei
AU - Machida, Shuichi
AU - Kobayashi, Hiroyuki
AU - Naito, Hisashi
AU - Cohen, Pinchas
AU - Fuku, Noriyuki
N1 - Funding Information:
This research was supported in part by JSPS KAKENHI Scientific Research (B) ( 18H03155 to N.F.), Young Scientists (A) ( 17H04752 to E.M.), Young Scientists ( 18K17863 to H.K.), and by the Institute of Health and Sports Science & Medicine, Juntendo University . This study was also supported in part by grants P01AG034906 and R01AG069698 to P.C.
Publisher Copyright:
© 2021
PY - 2022/2
Y1 - 2022/2
N2 - 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.
AB - 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.
KW - Genetic polymorphism
KW - MOTS-c
KW - Muscle fiber composition
KW - Muscular strength
KW - Sprint/power performance
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U2 - 10.1016/j.bbagen.2021.130048
DO - 10.1016/j.bbagen.2021.130048
M3 - Article
C2 - 34728329
AN - SCOPUS:85118568415
SN - 0304-4165
VL - 1866
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 2
M1 - 130048
ER -