Fig. 4: Molecular mechanisms regulating the divergent response to SIE.

A Exercise-induced increases in markers of the integrated stress response (ISR) (eIF2α phosphorylation at serine 52 [MICE n = 7; SIE n = 8]; and PPP1R15A mRNA [MICE n = 13; SIE n = 14]⁶⁸). B Time course of protein changes following moderate-intensity continuous exercise (MICE; n = 13 for pULK1 S556 and LC3B; n = 9 for p62) and sprint-interval exercise (SIE; n = 14 for pULK1 S556 and LC3B; n = 11 for p62) in key autophagy and mitophagy proteins. C Representative western blots from the proteins analyzed. Stain-free image shows consistent protein loading across samples. D Post-SIE micrograph showing swollen mitochondrial aggregates clustered together with an adjacent mitophagosome, and a mitochondrial degradation event. Scale bar = 0.5 µm. E Model for how SIE initiates a unique transcriptional signature through the sensing of mitochondrial stress by the ISR. * denotes group differences or main effect at p < 0.05; # denotes time × group interaction at p < 0.05. For A data are expressed as mean and for B as mean ± 95% confidence interval. For A and B differences between groups were assessed via two-way ANOVA with Sidak’s multiple comparison test. Source data are provided as a Source Data file.