Altered Ca2+ homeostasis in the skeletal muscle of DJ − 1 null mice

Loss-of-function mutations in DJ − 1 are associated with early-onset of Parkinson's disease. Although DJ − 1 is ubiquitously expressed, the functional pathways affected by it remain unresolved. Here we demonstrate an involvement of DJ − 1 in the regulation of Ca2+ homeostasis in mouse skeletal muscle. Using enzymatically dissociated flexor digitorum brevis muscle fibers from wild-type (wt) and DJ − 1 null mice, we examined the effects of DJ − 1 protein on resting, cytoplasmic [Ca2+] ([Ca2+]i) and depolarization-evoked Ca2+ release in the mouse skeletal muscle. The loss of DJ − 1 resulted in a more than two-fold increase in resting [Ca2+]i. While there was no alteration in the resting membrane potential, there was a significant decrease in depolarization-evoked Ca2+ release from the sarcoplasmic reticulum in the DJ − 1 null muscle cells. Consistent with the role of DJ − 1 in oxidative stress regulation and mitochondrial functional maintenance, treatments of DJ − 1 null muscle cells with resveratrol, a mitochondrial activator, or glutathione, a potent antioxidant, reversed the effects of the loss of DJ − 1 on Ca2+ homeostasis. These results provide evidence of DJ − 1's association with Ca2+ regulatory pathways in mouse skeletal muscle, and suggest the potential benefit of resveratrol to functionally compensate for the loss of DJ − 1.