Mitochondrial Respiration in Intact Peripheral Blood Mononuclear Cells and Sirtuin 3 Activity in Patients with Movement Disorders

OBJECTIVE Mitochondrial dysfunction is considered a unifying pathophysiological explanation for movement disorders. Sirtuin 3 (SIRT3) exhibits deacetylase activity and antioxidant properties. The aim of the study was to analyze the mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) and the SIRT3 activity in patients with movement disorders. METHODS Mitochondrial respiration was analyzed in intact PBMCs using the ROUTINE, LEAK, electron transfer system (ETS), and residual oxygen consumption (ROX) protocol by means of high-resolution respirometry. The SIRT3 expression and PBMC activity were measured using fluorometry. Ultrasound measurements of the echogenicity of the substantia nigra and the diameter of the 3rd ventricle were also performed. RESULTS Patients with movement disorders exhibited a lower ROUTINE respiration than controls (P = 0.0237). Reduced oxygen fluxes in the LEAK (P = 0.033) and ROX (P = 0.0486) states were observed in patients with movement disorders compared with controls. Decreased ROUTINE respiration (P = 0.007) and oxygen flux in the LEAK state (P = 0.0203) were observed in patients with PD with substantia nigra hyperechogenicity compared with controls. Decreased SIRT 3 deacetylase activity was found in patients with movement disorders. CONCLUSION Impaired mitochondrial respiration in intact PBMCs was associated with inhibited SIRT3 activity and neurodegeneration measures evaluated using ultrasound in patients with PD.