AB0176 Mitochondrial dysfunction in idiopathic inflammatory myopathy derived myoblasts

Background Idiopathic inflammatory myopathies (IIM) are acquired skeletal muscle diseases, characterized by proximal muscle weakness. This syndrome includes five different (1) diseases, nevertheless, in this work, we included dermatomyositis (DM) and polymyositis (PM) patients. Has been reported that despite treating inflammation, muscle atrophy and weakness persist in some patients, suggesting an inherent muscle cause (2,3). In addition, histological studies show some mitochondrial abnormalities. Our aim was to evaluate a possible role for mitochondrial dysfunction in the pathophysiology of this diseases. Objectives To compare the mitochondrial status of myoblast obtained from myositis patients -and healthy control- biopsies. Methods Primary cultured myoblasts extracted from the deltoid of IIM patients were used and compared with myoblasts obtained from normal patients subjected to shoulder surgery. Also, a human skeletal muscle cell line (RCMH) was used as control. The bioenergetic profile was analyzed with an Extracellular flux analyzer e 96 (Seahorse Biosciences). Also, biopsy tissue was used for Western blot (WB) and immunofluorescence experiments. Results Basal oxygen consumption rate, ATP-linked oxygen consumption, maximal oxygen consumption and spare respiratory capacity were lower in IIM myoblasts when compared to RCMH myoblasts, however, when compare to control primary cultured myoblasts we only find differences in ATP-linked oxygen consumption. Expression levels of mitochondrial complexes (I, III, IV and V) were analyzed by WB in tissue samples. No differences were observed between control and IIM patients. Mitochondrial area was estimated by immunofluorescence of the voltage dependent anion channel (VDAC), which show no differences between control and patients. Conclusions IIM derived myoblasts present a compromised mitochondrial function, compared to control myoblasts. Specially, oxygen consumption associated with ATP synthesis show decreased levels in patients. Although, expression levels of the mitochondrial complexes as well as mitochondrial area were not different between control and patients. Future experiments should address if IIM mitochondria are consuming less oxygen because of a lower ATP demand or because a primary mitochondrial damage. References Dalakas M. Inflammatory Muscle Diseases. N Engl J Med. 372:1734–1747, 2015. Park, J. H. et al. Magnetic resonance imaging and P-31 magnetic resonance spectroscopy provideunique quantitative data useful in the longitudinal management of patients with dermatomyositis. Arthritis Rheum.37, 736–46, 1994. Lee, H.-K. et al. Foxo/Atrogin induction in human and experimental myositis. Neurobiol. Dis.46, 463–475, 2012. Acknowledgements FONDECYT 3150623 & 1151383; FONDAP 15150012. Disclosure of Interest None declared