A Single Dose of Exercise Initiates Corrective Mitochondrial Plasticity in Myotonic Dystrophy Type 1
Bibliographic record
Abstract
Myotonic dystrophy type 1 (DM1) is the most common life‐limiting muscular dystrophy in adults. Abnormal mitochondrial function and dynamics have been observed in DM1 patient derived cells, which likely exacerbates the muscle pathology in DM1. Exercise is safe, low‐cost, and accessible medicine that reaps robust benefits to mitochondrial biology. However, in DM1 muscle, in vivo assessments of mitochondrial dynamics and mitophagy, as well as the effects of exercise therein, remain unexamined. Therefore, this study aims to further elucidate mitochondrial properties in a mouse model of DM1 (HSA LR ) and examine the mitochondrial response following an acute bout of exercise. Both wild‐type (WT) and HSA LR mice performed a progressive, vigorous bout of exercise on a treadmill until the inability to continue running was objectively determined. Muscle samples were collected at rest and at various timepoints following exercise. At rest, phosphorylated dynamin‐related protein 1 (p‐DRP1 Ser616 ), total DRP1 and Parkin levels were elevated (p < 0.05) in HSA LR mice compared to WT. Furthermore, the mitofusin‐2 (MFN2)‐to‐DRP ratio was significantly lower in HSA LR animals relative to their WT counterparts. Exercise capacity was lower (p < 0.05) in HSA LR mice compared to WT. Immediately following exercise, p‐DRP1 Ser616 levels were significantly increased in WT animals but returned to the resting state at 3 hours post‐exercise. In contrast, HSA LR showed elevated (p < 0.05) p‐DRP1 Ser616 until 3 hours post‐exercise before returning to basal levels at 12 hours. Mitochondrial fission 1 (Fis1) protein content significantly increased 3 hours post‐exercise in WT animals and 12 hours post‐exercise in the HSA LR group. MFN2 content was augmented (p < 0.05) immediately following exercise and remained elevated up to 24 hours in HSA LR mice only, thus, restoring the MFN2‐to‐DRP1 ratio. Lastly, fission and mitophagy related mRNA transcripts were blunted immediately and 3 hours (p < 0.05) following exercise while the transcription of fusion related genes was augmented (p < 0.05). In contrast, the expression of mitophagy related genes was significantly increased 12 and 24 hours following the exercise bout. Collectively, these data provide further evidence for mitochondrial dysfunction within DM1 biology. An imbalance in fusion and fission processes could greatly diminish mitochondrial function, which could in turn accelerate skeletal muscle atrophy. Exercise may be a promising intervention to correct the imbalance in mitochondrial dynamics and augment overall mitochondrial function within DM1 muscle.
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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) | 0.001 | 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 | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".