Altering aspects of mitochondrial quality to improve musculoskeletal outcomes in disuse atrophy---Supplementary Figure 1 Confirmation of Genotype
Figure 1: Confirmation
of genotype for both PGC1α and MCAT colonies. A: Representative images
from genotyping of PGC1α mice using ethidium bromide gels. B: Pgc1α mRNA
content C: PGC1-α protein content. D: Representative images from
genotyping of MCAT mice using ethidium bromide gels. E: Catalase
mRNA content in the gastrocnemius muscles. F: Catalase mRNA
content in the soleus muscles. * denotes p<0.05. PGC males had the following
sample sizes: WT-CON= 9, WT-HU= 10, PGC-CON= 9, PGC-HU= 9. PGC females had the
following samples sizes: WT-CON= 8, WT-HU= 9, PGC-CON= 9, PGC-HU= 9. MCAT males
had the following sample sizes: WT-CON= 8, WT-HU= 7, MCAT-CON= 4, MCAT-HU= 3. MCAT
females had the following samples sizes: WT-CON= 5, WT-HU= 6, MCAT-CON= 6,
Article Title: Altering aspects of mitochondrial quality to improve musculoskeletal outcomes in disuse atrophy
Authors: Megan E. Rosa-Caldwell, Seongkyun Lim, Wesley S. Haynie, Lisa T. Jansen, Lauren C. Westervelt, Madeline G. Amos, Tyrone A. Washington, Nicholas P. Greene
Abstract: Muscle atrophy is a significant moderator for disease prognosis; as such, interventions to mitigate disuse-induced muscle loss are imperative to improve clinical interventions. Mitochondrial deteriorations may underlie disuse-induced myopathies; therefore, improving mitochondrial quality may be an enticing therapeutic intervention. However, different mitochondrial-based treatments may have divergent impacts on the prognosis of disuse atrophy. Therefore, the purpose of this study was to investigate different mitochondria-centered interventions during disuse atrophy in hindlimb unloaded male and female mice. Methods: Male and female mice overexpressing PGC-1α (PGC-1α) or mitochondrially-targeted catalase (MCAT) and their respective wildtype (WT) littermate controls were hindlimb unloaded for 7 days to induce disuse atrophy or allowed normal ambulatory activity (cage control; CON). After designated interventions, animals were euthanized and tissues collected for measures of mitochondrial quality control and protein turnover. Results: While PGC-1α overexpression mitigated ubiquitin-proteasome activation (MuRF1 and Atrogin mRNA content), this did not correspond to phenotypic protections from disuse-induced atrophy. Rather, PGC-1α mice appeared to have a greater reliance on autophagic protein breakdown compared to WT. In MCAT mice, females exhibited a mitigated response to disuse atrophy; however, this effect was not noted in males. Despite these phenotypic differences, there were no clear cellular signaling differences between MCAT hindlimb unloaded females and MCAT fully loaded females. Conclusion: PGC-1α overexpression does not protect against phenotypic alterations during disuse atrophy but appears to shift catabolic pathways moderating atrophy. However, increased mitochondrially-targeted catalase activity appears to blunt disuse atrophy within highly oxidative muscles specifically in female mice.
Mitochondrial Degeneration ? the Root of Skeletal Muscle Atrophy
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