A19 High-resolution respirometry as a tool to assess skeletal muscle mitochondrial state in patients with huntington’s disease

Abstract

Background Along with the affected nervous system, muscle pathology stands out as a well-recognized hallmark of Huntington’s disease (HD) and manifested in muscle wasting, atrophy, and accompanied by defects in energy metabolism. High-resolution respirometry (HRR) can be considered a promising tool to determine alterations in mitochondrial function in premanifest and manifest HD patients. Aims To determine the feasibility of HRR in the assessment of skeletal muscle mitochondrial function in patients with HD. Methods Muscle samples were acquired by a fine-needle biopsy method from the middle part of the m. rectus femoris of 8 HD premanifest patients (age, mean ± SD, 27 ± 3.25 years), 8 manifest patients (43.1 ± 5.59 years), and 15 age and sex-matched controls (28.5 ± 3.21 years, matched to premanifest; 40.3 ± 5.59 years, matched to manifest). After mechanical preparation and permeabilization with saponin, changes in mtMP (mitochondrial membrane potential) were assessed simultaneously with respiration measurement using cell-permeant, cationic dye TMRM (tetramethylrhodamine, methyl ester), and HRR system Oroboros Oxygraph-2k (Oroboros Instruments, Austria). The data were normalized to the wet weight of samples; results (pmol O2/s/mg, means ± SD) were statistically analyzed using the Mann-Whitney test. Results The coupled respiration rates (both CI- and CI+CII-related respiration during oxidative phosphorylation) were lower in premanifest patients when compared to matched controls and manifests (CI: 20.7 ± 2.7 vs. 26.6 ± 2.0 and 27.9 ± 6.5, p Conclusions HRR can be used to assess mitochondrial state in skeletal muscles from patients with HD.