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.