P 166 - Ultrastructural Assessment of Mitochondrial Network in the Cultured Skin Fibroblasts from Patients Harboring tRNA Mutations

Abstract

Single-point mutation of mitochondrial DNA (mtDNA) has been confirmed to be involved in some inheritance of mitochondrial myopathy such as Mitochondrial Encephalopathy, Lactic acidosis, And Stroke-like syndrome (MELAS) and Myoclonic Epilepsy and Ragged-Red Fibers (MERRF). The A-to-G mutation at nucleotide 8344 accounts for 80 to 90% of MERRF syndrome. More than 80% of MELAS patients carry the A3243G mutation. The location of these two point mutations were identified in the transfer RNA (tRNA). It remains unknown why these particular tRNA point mutations caused the abnormal phenotypes. Some studies have demonstrated that Reactive Oxygen Species (ROS) production, alteration in antioxidant defenses and detoxification enzymes is involved in the pathogenesis of MERRF and MELAS syndrome. More and more reports revealed a potential role of oxidative stress within dysregulated mitochondrial network in lesion tissue. However, structural integrity and appropriate distribution and dynamics of mitochondria have to be maintained to execute normal physiological functions. Therefore, we integrated light and electron microscopy to illuminate mosaic mechanisms of the altered mitochondrial distribution and dynamics in cultured skin fibroblasts from patients with mitochondrial tRNA mutations.