Acute treadmill exercise induces mitochondrial unfolded protein response in skeletal muscle of male rats

• Published in: Biochimica et biophysica acta. Bioenergetics 2024-12, Vol.1866 (2), p.149532, Article 149532
• Main Authors: Turkel, Ibrahim, Kubat, Gokhan Burcin, Fatsa, Tugba, Acet, Ozgu, Ozerklig, Berkay, Yazgan, Burak, Simsek, Gulcin, Singh, Keshav K., Kosar, Sukran Nazan
• Format: Article
• Language: English
• Subjects: Exercise; Mitochondria; Mitochondrial proteostasis; Mitochondrial unfolded protein response; Skeletal muscle; UPRmt
• ISSN: 0005-2728; 1879-2650; 1879-2650
• DOI: 10.1016/j.bbabio.2024.149532

Mitochondria are often referred to as the energy centers of the cell and are recognized as key players in signal transduction, sensing, and responding to internal and external stimuli. Under stress conditions, the mitochondrial unfolded protein response (UPRmt), a conserved mitochondrial quality control mechanism, is activated to maintain mitochondrial and cellular homeostasis. As a physiological stimulus, exercise-induced mitochondrial perturbations trigger UPRmt, coordinating mitochondria-to-nucleus communication and initiating a transcriptional program to restore mitochondrial function. The aim of this study was to evaluate the UPRmt signaling response to acute exercise in skeletal muscle. Male rats were subjected to acute treadmill exercise at 25 m/min for 60 min on a 0 % grade. Plantaris muscle were collected from both sedentary and exercise groups at various times: immediately (0), and at 1, 3, 6, 12, and 24 h post-exercise. Reactive oxygen species (ROS) production was assessed using hydrogen peroxide assay and dihydroethidium staining. Additionally, the mRNA and protein expression of UPRmt markers were measured using ELISA and real-time PCR. Mitochondrial activity was assessed using succinate dehydrogenase (SDH) and cytochrome c oxidase (COX) staining. Our results demonstrated that acute exercise led to increased ROS production and upregulation of UPRmt markers at both gene and protein levels. Moreover, skeletal muscle exhibited an increase in mitochondrial activity in response to exercise, as indicated by SDH and COX staining. These findings suggest that acute treadmill exercise is sufficient to induce ROS production, activate UPRmt signaling, and enhance mitochondrial activity in skeletal muscle, expanding our understanding of mitochondrial adaptations to exercise. [Display omitted] •The mitochondrial unfolded protein response (UPRmt) is a stress response that maintains mitochondrial homeostasis through retrograde (mitonuclear) signaling.•Reactive oxygen species production increases in skeletal muscle following acute exercise.•Acute exercise induces the expression of UPRmt-related genes and proteins in skeletal muscle.•Succinate dehydrogenase and cytochrome c oxidase staining increase in skeletal muscle following acute exercise.