Downhill running induced mitophagy in rat soleus muscle via the AMPK pathway.

Eccentric exercise is known to induce more pronounced muscle damage associated with delayed-onset muscle soreness than concentric exercise. This study aimed to investigate whether AMP-activated protein kinase (AMPK) pathway participates in control of mitophagy in rat skeletal muscle in response to downhill running. Eighty-eight male Sprague-Dawley rats were exercised on a treadmill tilted at 16° decline at 16 m·min^- 1 for 90 min, with the soleus muscle sampled at 0 h, 12 h, 24 h, 48 h and 72 h after exercise. The AMPK inhibitor compound C or AMPK activator AICAR or saline was injected intraperitoneally 20 min before exercise. After downhill treadmill running, the skeletal muscle mitochondrial structure appeared to be abnormal and contained mitophagosomes; the expression levels of AMPK phosphorylation, cyclophilin D (CypD), cytochrome C (CytC), mitochondrial FK506-binding protein 8 (FKBP8), microtubule-associated protein 1 light chain 3 (LC3), and the co-localization of FKBP8 with LC3 and mitochondria with dynamin-related protein 1 (Drp1), lysosomal-associated membrane protein 2 (LAMP2) were significantly higher; the expression levels of mechanistic target of rapamycin (mTOR Ser2448) phosphorylation and heat shock protein 60 (HSP60), mitochondrial respiratory complex I (NDUFB8) and complex III (UQCRC2), and adenosine triphosphate (ATP) content were significantly lower than those in the C group. Further study showed that the effect of downhill treadmill running was partly blocked by compound C and strengthened by AICAR. A session of downhill treadmill running activated the AMPK pathway and promoted LC3 co-localizations with mitochondria and FKBP8, and induced mitophagy and mitochondrial damage within rat skeletal muscle.