Biology subjects

Perri, E.

Publications and source records attributed to Perri, E..

3 recordsLinked to original sources

bioRxiv2024

Sprint interval exercise disrupts mitochondrial ultrastructure driving a unique mitochondrial stress response and remodelling in humans

Exercise remains the most effective lifestyle intervention to remodel the mitochondrial network and to prevent most non-communicable diseases. Despite this, the molecular mechanisms by which different exercise prescriptions dictate mitochondrial remodelling are poorly understood in humans. Here, we show that, compared to moderate-intensity continuous exercise (MICE), sprint-interval exercise (SIE) - a known time-efficient high-intensity exercise - leads to mitochondrial stress and activates the mitochondrial unfolded protein response (UPRmt). The SIE-specific signature is characterized by a morphological and ultrastructural mitochondrial disturbance, concurrent with the activation of the integrated stress response (ISR) and mitochondrial quality control (MQC) pathways. When the respective exercises are repeated over time (8 weeks), our results demonstrate that moderate-intensity continuous training (MICT) and sprint-interval training (SIT) lead to a divergent mitochondrial remodelling. MICT elicits a mitochondrial adaptation characterized by an increase in markers of mitochondrial content, complex I activity, and enrichment of proteins involved in tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS) system. On the other hand, SIT leads to proteomic enrichment of pathways involved in mitochondrial 1-Carbon metabolism and protein quality control, concurrently with improvements in mitochondrial respiratory function. Lastly, we have identified COX7A2L as a divergently regulated protein across groups, significantly accumulating in III2+IV1 respiratory supercomplexes only following SIT. In conclusion, our study provides mechanistic insights on how SIE and MICE divergently impact the post-exercise mitochondrial signalling, and subsequent long-term mitochondrial remodelling following training. These findings provide a strong basis for targeted exercise prescription to modulate specific mitochondrial adaptations in human skeletal muscle.

molecular biology↗

bioRxiv2021

Exercise and training regulation of autophagy markers in human and rodent skeletal muscle.

Autophagy is a key intracellular mechanism by which cells degrade old or dysfunctional proteins and organelles. In skeletal muscle, evidence suggests that exercise increases autophagosome content and autophagy flux. However, the exercise-induced response seems to differ between rodents and humans, and little is known about how different exercise prescription parameters may affect these results. The present study utilised skeletal muscle samples obtained from four different experimental studies using rats and humans. Here we show that following exercise, in the soleus muscle of Wistar rats, there is an increase in LC3B-I protein levels (+ 109%) immediately after exercise, and a subsequent increase in LC3B-II protein levels (+ 97%) 3 hours into the recovery. Conversely, in human skeletal muscle, there is an immediate exercise-induced decrease in LC3B-II protein levels (- 24%), independent of whether exercise is performed below or above the maximal lactate steady state, which returns to baseline 3.5 hours following recovery, while no change in LC3B-I protein levels is observed. p62 protein levels did not change in neither rats nor humans following exercise. By employing an ex vivo autophagy flux assay previously used in rodents we demonstrate that the exercise-induced decrease in LC3B-II protein levels in humans does not reflect a decreased autophagy flux. Instead, effect size analyses suggest a modest-to-large increase in autophagy flux following exercise that lasts up to 24 hours. Our findings suggest that exercise-induced changes in autophagosome content markers differ between rodents and humans, and that exercise-induced decrease in LC3B-II protein levels do not reflect autophagy flux level.

molecular biology↗

bioRxiv2019

Exercise twice-a-day potentiates skeletal muscle signalling responses associated with mitochondrial biogenesis in humans, which are independent of lowered muscle glycogen content

Endurance exercise begun with reduced muscle glycogen stores seems to potentiate skeletal muscle protein abundance and gene expression. However, it is unknown whether this greater signalling responses is due to low muscle glycogen per se or to performing two exercise sessions in close proximity - as a first exercise session is necessary to reduce the muscle glycogen stores. In the present study, we manipulated the recovery duration between a first muscle glycogen-depleting exercise and a second exercise session, such that the second exercise session started with reduced muscle glycogen in both approaches but was performed either two or 15 h after the first exercise session (so-called "twice-a-day" and "once-daily" approaches, respectively). We found that exercise twice-a-day increased the nuclear abundance of transcription factor EB (TFEB) and nuclear factor of activated T cells (NFAT) and potentiated the transcription of peroxisome proliferator-activated receptor-coactivator 1 alpha (PGC-1), peroxisome proliferator-activated receptor alpha (PPAR) and peroxisome proliferator-activated receptor beta/delta (PPAR{beta}/{delta}) genes, in comparison with the once-daily exercise. These results suggest that the elevated molecular signalling reported with previous "train-low" approaches can be attributed to performing two exercise sessions in close proximity rather than the reduced muscle glycogen content per se. The twice-a-day approach might be an effective strategy to induce adaptations related to mitochondrial biogenesis and fat oxidation.

molecular biology↗