SS-31 Reverses Mitochondrial Fragmentation in Fibroblasts from Patients with DCMA, a Mitochondrial Cardiomyopathy

We used patient dermal fibroblasts to characterize the mitochondrial abnormalities associated with the dilated cardiomyopathy with ataxia syndrome (DCMA) and to study the effect of the mitochondrially-targeted peptide SS-31 as a potential novel therapeutic. Overall design: Dermal fibroblasts from four pediatric patients with DCMA were used to establish parameters of mitochondrial dysfunction. Mitochondrial structure, reactive oxygen species (ROS) production, cardiolipin composition and gene expression were evaluated. Total RNA was extracted from DCMA fibroblasts (n=4) and control fibroblasts (n=4) using the RNA extraction Mini kit (Invitrogen) according to the manufacturer's protocol. The sequencing library was prepared using 2 µg of RNA and the TruSeq Stranded mRNA library preparation kit (Illumina) on NextSeq500 platform. RNA-Seq identifies changes in gene expression related to DCMA. Comparison between DCMA and control fibroblasts identified 288 transcripts that were significantly differentially-expressed . However, there were five transcripts that were highly significantly different. Implicated genes of particular note included DNAJC19 and those involved in oxidative stress (GSTM1) and mitochondrial biogenesis (GATD3A).