Exercise-induced mitochondrial biogenesis coincides with the expression of mitochondrial translation factors in murine skeletal muscle

Abstract

The process of mitochondrial translation, in which mitochondrial (mt)DNA-encoded genes are translated into proteins, is crucial for mitochondrial function and biogenesis. In each phase, a series of mitochondrial translation factors is required for the synthesis of mtDNA-encoded mitochondrial proteins. Two mitochondrial initiation factors (mtIF2 and mtIF3), three mitochondrial elongation factors (mtEFTu, mtEFTs, and mtEFG1), one mitochondrial release factor (mtRF1L), and two mitochondrial recycling factors (mtRRF1 and mtRRF2) are mitochondrial translation factors that coordinate each translational phase. Exercise increases both nuclear DNA- and mtDNA-encoded mitochondrial proteins, resulting in mitochondrial biogenesis in skeletal muscles. Therefore, mitochondrial translation factors are likely regulated by exercise; however, it is unclear whether exercise affects mitochondrial translation factors in the skeletal muscles. We investigated whether exercise training comprehensively increases this series of mitochondrial translation factors, as well as mtDNA-encoded proteins, in the skeletal muscle. Mice were randomly assigned to either the sedentary or exercise group and housed in standard cages with or without a running wheel for 1 and 8 weeks. The expression levels of mitochondrial translation factors in the plantaris and soleus muscles were then measured. Exercise training concomitantly upregulated mitochondrial translation factors and mitochondrial proteins in the plantaris muscle. However, in the soleus muscle, these comprehensive upregulations were not detected. These results indicate that exercise-induced mitochondrial biogenesis coincides with the upregulation of mitochondrial translation factors.

Keywords: Mitochondrial translation factor; exercise; mitochondrial biogenesis; skeletal muscle.

Figure 1

Protein expressions of mitochondrial translation factors in metabolically heterogeneous muscles. Representative image and quantification of mitochondrial proteins (A), mitochondrial translation factors (B and C), and CBB staining (D). Values are mean ± SEM; dot plot represents individual data points; n = 3 per group.

Figure 2

Correlation between the content of mtDNA‐encoded proteins and expression of mitochondrial translation factors in metabolically heterogeneous muscles. (A) Scatterplots show the levels of MTCO1 versus those of mitochondrial translation factors in the gastrocnemius (GA), plantaris (PLA), soleus (SOL), extensor digitorum longus (EDL), and tibias anterior (TA) muscles. (B) Scatterplots show the levels of MTCO1 versus the average expression of initiation factors, elongation factors, and recycling factors and total expression of all factors in GA, PLA, SOL, EDL, and TA muscles. The shaded areas show 95% confidence limits of the fitted line. n = 3 per group. ***P < 0.001.

Figure 3

Effects of 8‐week exercise training on the expression of mitochondrial proteins and mitochondrial translation factors in the plantaris and soleus muscles. Body weight (A), body weight change (B), and muscle weight (C) in sedentary mice (Sed) and exercised mice (Ex). (D–G) Representative immunoblots and quantifications of OXPHOS protein levels (D and E) and those of mitochondrial translation factors (F and G) in the plantaris and soleus muscles of sedentary and exercised groups of mice. (J and K) Representative images and quantifications of Coomassie brilliant blue (CBB) staining. Values are mean ± SEM; dot plot represents individual data points; n = 6 per group. *P < 0.05 vs. Sed. **P < 0.01 vs. Sed. ***P < 0.001 vs. Sed.

Figure 4

Correlation between the levels of mtDNA‐encoded protein MTCO1 and mitochondrial translation factors in the plantaris muscle of sedentary mice (Sed) and mice exercised for 8 weeks (Ex). (A) Scatterplots showing the levels of MTCO1 versus those of mitochondrial translation factors. (B) Scatterplots showing the levels of MTCO1 versus average levels of initiation factors, elongation factors, and recycling factors and total levels of all the factors. The shaded areas show 95% confidence limits of the fitted line. n = 6 per group. **P < 0.01. ***P < 0.001.

Figure 5

Effects of 1‐week exercise training on the expression of mitochondrial proteins and mitochondrial translation factors in the plantaris and soleus muscles. Body weight (A), body weight change (B), and muscle weight (C) in sedentary mice (Sed) and exercised mice (Ex). (D–G) Representative immunoblots and quantifications of OXPHOS protein levels (D and E) and those of mitochondrial translation factors (F and G) in the plantaris and soleus muscles of sedentary and exercised groups of mice. (J and K) Representative images and quantifications of Coomassie brilliant blue (CBB) staining. Values are mean ± SEM; dot plot represents individual data points; n = 6 per group. *P < 0.05 vs. Sed. **P < 0.01 vs. Sed. ***P < 0.001 vs. Sed.

Figure 6

Correlation between the levels of mtDNA‐encoded protein MTCO1 and those of mitochondrial translation factors in the plantaris muscles of sedentary mice (Sed) and mice exercised for 1 week (Ex). (A) Scatterplots of the levels of MTCO1 versus those of mitochondrial translation factors. (B) Scatterplots of the levels of MTCO1 versus average levels of initiation factors, elongation factors, and recycling factors and total levels of all the factors. The shaded areas show 95% confidence limits of the fitted line. n = 6 per group. *P < 0.05 vs. Sed. **P < 0.01. ***P < 0.001.