The Effect of Chronic Contractile Activity and Retinoic Acid on Mitochondrial Turnover in C2C12 Myotubes
Bibliographic record
Abstract
Mitochondrial turnover is necessary for the optimization and maintenance of a healthy pool of functional organelles, able to meet the metabolic needs of the muscle cell. Exercise is known to improve mitochondrial turnover by activating both mitochondrial biogenesis and mitochondrial‐specific autophagy, known as mitophagy. Moreover, research in adipocytes and liver tissue has shown the potential of the dietary supplement retinoic acid to activate mitochondrial biogenesis as well. Retinoids have also been shown to be effective in activating autophagy in cancer cells. However, the combined effect of retinoic acid isomers and exercise in facilitating mitochondrial turnover has not been described. The purpose of this project was to evaluate the effect of retinoic acid (RA) isomers combined with exercise on muscle mitochondrial turnover. Mouse C2C12 myoblasts were plated on 6‐well plates and allowed to differentiate into myotubes. Myotubes were then treated with either vehicle (DMSO), or the retinoic acid (RA) isomers 9‐cis RA or All‐trans RA (ATRA) in the absence or presence of electrical stimulation to elicit Chronic Contractile Activity (CCA; 4days, 3hrs/day). Sample collection took place 21h after the fourth day. Mitochondrial biogenesis was assessed by examining the protein content of PGC‐1α, as well as nuclear and mitochondrially‐encoded mitochondrial proteins. CCA led to a 3‐fold increase in COX subunit IV expression, as well as a 2‐fold increase in PGC‐1α. The mtDNA‐encoded COX subunit I was modestly changed by CCA, but increased 2‐fold in response to 9cis‐RA or ATRA treatment. These RA isomers also increased PGC‐1α by 3‐fold, but had no significant impact on COX IV expression. When RA isomers were combined with CCA, no additive or synergistic effects were observed. To evaluate mitochondrial degradation, we examined several lysosomal and mitophagy proteins. While autophagy proteins Beclin and p62 showed no changes with CCA or RA treatment, the LC3II to LC3I ratio was reduced 2‐fold with CCA, suggesting an enhanced clearance of autophagosomes. RA isomers had no effect on this ratio. The lysosomal fusion protein Lamp1 was increased 1.8‐fold by ATRA, but not further by CCA. Our data suggest that while RA isomers and CCA both promote mitochondrial biogenesis, RA appears to target mitochondrially‐encoded proteins, while CCA appears to have greater effects on the expression of target nuclear‐encoded proteins. CCA also may serve as a stimulus for the clearance of autophagosomes containing damaged cargo. The lack of synergy among these pathways suggests that they operate independently to stimulate mitochondrial turnover. Support or Funding Information Supported by NSERC, Canada This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".