F089 Mitochondrial parameters in peripheral tissues in early stages of Huntington´s disease

<h3>Background</h3> Our previous investigation showed impairment of mitochondrial parameters in peripheral blood mononuclear cells (PBMC) and cultivated skin fibroblasts of symptomatic HD (s-HD) patients. The aim was to investigate selected mitochondrial parameters in pre-symptomatic (pre-HD) and early (early-HD) stages of HD. Study cohort consists of genetically confirmed HD patients: 9 patients in pre-HD, 12 in early early-HD and 21 in s-HD stage of the disease and 21 age-related controls. The CAG repeats were 41.9 ± 1.3 in pre-HD, 45.9 ± 4.3 in early-HD and 45.3 ± 2.9 for the s-HD stage. <h3>Methods</h3> Activities of respiratory chain complexes (RCC) I, II and IV and citrate synthase (CS), and protein expression were analyzed by spectrophotometry and western blot. Mitochondrial respiration and glycolytic activity in fibroblasts were measured by Seahorse, metabolic turnover using substrate oxidation (SO). Ultrastructure of mitochondria was studied by transmission electron microscopy. <h3>Results</h3> In PBMC, activity of RCC II was significantly increased in all patient groups compared to controls. RCC IV activity (including ratio CIV/CS) was decreased even in pre-HD patients. Decreased COX2 subunit of RCC IV and SDH70 subunit of RCC II were found in pre- and early-HD. HD mitochondria showed lower number of cristae compared to controls. In fibroblasts, pre- and early-HD had increased maximal respiration. SO revealed a decrease of pyruvate oxidation rate in pre-HD. <h3>Conclusion</h3> Selected mitochondrial parameters in peripheral tissues are disturbed before the onset of clinical symptoms in HD patients, and prior to impairment in PBMC DNA. <h3>Supported by</h3> Cooperatio program in Paediatrics and AZV MZ CR NU20-04-00136