Mots-C
Mitochondrial open reading frame of the 12S rRNA-c, MT-RNR1, Mitochondrial-derived peptide MOTS-c
The MOTS-c K14Q polymorphism in the mtDNA is associated with muscle fiber composition and muscular performance.
Kumagai. Hiroshi H; Natsume. Toshiharu T; Kim. Su-Jeong SJ; Tobina. Takuro T; Miyamoto-Mikami. Eri E; Shiose. Keisuke K; Ichinoseki-Sekine. Noriko N; Kakigi. Ryo R; Tsuzuki. Takamasa T; Miller. Brendan B; Yen. Kelvin K; Murakami. Haruka H; Miyachi. Motohiko M; Zempo. Hirofumi H; Dobashi. Shohei S; Machida. Shuichi S; Kobayashi. Hiroyuki H; Naito. Hisashi H; Cohen. Pinchas P; Fuku. Noriyuki N
Key Findings
- The K14Q MOTS‑c variant (C allele) is associated with a higher proportion of fast‑twitch (MHC‑IIx) muscle fibers in Japanese individuals.
- Men carrying the C allele show greater peak torque in leg flexion and extension, indicating stronger power output.
- The C allele is more common in sprint/power athletes than in endurance athletes or controls, and neutralizing MOTS‑c in mice increases fast‑fiber protein expression.
Practical Outcomes
- If you aim for power and sprint performance, reducing MOTS‑c activity (e.g., via genetics or possibly antagonists) might help shift muscle toward fast fibers. Conversely, supplementing MOTS‑c could promote slow‑twitch fibers and endurance, which may benefit metabolic health and longevity. No specific dosing protocol is provided, but the study suggests MOTS‑c modulation as a potential tool for tailoring muscle phenotype.
Summary
A common East Asian genetic variant (K14Q) that weakens the MOTS‑c peptide is linked to more fast‑twitch muscle fibers and better sprint/power performance, while higher MOTS‑c activity may favor slower, endurance‑type fibers. In mice, blocking MOTS‑c also boosted fast‑fiber proteins, supporting the human data.
Abstract
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.
Study Information
pubmed
2021
2021-10-30T00:00:00.000Z
10.1016/j.bbagen.2021.130048
11
24