PO-01-124 THE CALCIUM HANDLING MACHINERY IS REMODELED IN FRIEDREICH’S ATAXIA

Friedreich's ataxia (FA) is an inherited neurodegenerative disorder that causes progressive nervous system damage. FA caused by a deficiency in the frataxin protein due to expansion of GAA repeats first intron gene. Reduced expression thought negatively affect mitochondrial function, leading increased oxidative Although considered disorder, it not completely understood why most patients present with left ventricular systolic dysfunction and die from cardiac events. The objective our study determine whether abnormal calcium handling machinery molecular mechanism perpetuates FA. We used knock-out (KO) mouse model as well human heart samples donors unaffected donors. proteins was assessed proteomics western blot. In myocytes KO WT mice, IonOptix for imaging, seahorse assay utilized measure oxygen consumption rate (OCR) confocal imaging quantify membrane potential (Δψm), reactive species (ROS). ECG echocardiography were assess function mice. proteomic analysis blot, SERCA2, Ryr2 CaMKII significantly downregulated, voltage-dependent anion channel uniporter upregulated tissue humans On ECG, RR, PR, QRS, QTc intervals longer Echocardiography showed ejection fraction fractional shortening decreased wall thickness diameter Moreover, transient decay prolonged mice compared WT. Additionally, Δψm depolarized, OCR decreased, ROS levels elevated development contractile associated reduced proteins, cycling, dysfunction.