Abstract 313: Sphingosine-1-Phosphate and RhoA Signaling Regulate Dynamin-Related Protein 1 and Cardiac Mitochondrial Fission

In cardiomyocytes, signaling through RhoA is protective against ischemia/reperfusion injury. Cardioprotective receptor agonists such as sphingosine-1-phosphate (S1P) provide protection through RhoA activation. Mitochondrial fission has been suggested to play a role in cardioprotection, allowing for selective degradation of smaller damaged mitochondria. Our previous studies showed that RhoA signaling can protect cardiomyocytes against ischemia/reperfusion injury by blocking mitochondrial death pathways under oxidative stress, however it is not known if RhoA activation also regulates mitochondrial quality control. We tested the possibility that activated RhoA regulates cardiac mitochondrial fission. Adenoviral expression of constitutively active RhoA in cardiomyocytes caused an increase in small, fragmented mitochondria observed by both fluorescent confocal microscopy and electron microscopy. This mitochondrial fission phenotype was attenuated by inhibition of the downstream RhoA target Rho-associated Prote...