Supplementary Material for: Resistance Exercise Improves Mitochondrial Quality Control in a Rat Model of Sporadic Inclusion Body Myositis

<b><i>Background:</i></b> Mitochondrial dysfunction is implicated in the pathogenesis of multiple muscular diseases, including sporadic inclusion body myositis (s-IBM), the most common aging-related muscle disease. However, the factors causing mitochondrial dysfunction in s-IBM are unknown. <b><i>Objective:</i></b> We hypothesized that resistance exercise (RE) may alleviate muscle impairment by improving mitochondrial function via reducing amyloid-beta (Aβ) accumulation. <b><i>Methods:</i></b> Twenty-four male Wistar rats were randomized to a saline-injection control group (sham, <i>n</i> = 8), a chloroquine (CQ) control group (CQ-CON, <i>n</i> = 8), and a CQ plus RE group (CQ-RE, <i>n</i> = 8) in which rats climbed a ladder with weight attached to their tails 9 weeks after starting CQ treatment. <b><i>Results:</i></b> RE markedly inhibited soleus muscle atrophy and muscle damage. RE reduced CQ-induced Aβ accumulation, which resulted in decreased formation of rimmed vacuoles and mitochondrial-mediated apoptosis. Most importantly, the decreased Aβ accumulation improved both mitochondrial quality control (MQC) through increased mitochondrial biogenesis and mitophagy, and mitochondrial dynamics. Furthermore, RE-mediated reduction of Aβ accumulation elevated mitochondrial oxidative capacity by upregulating superoxide dismutase-2, catalase, and citrate synthase via activating sirtuin 3 signaling. <b><i>Conclusion:</i></b> RE enhances mitochondrial function by improving MQC and mitochondrial oxidative capacity via reducing Aβ accumulation, thereby inhibiting CQ-induced muscle impairment, in a rat model of s-IBM.