ABCB10 deletion in cardiomyocytes leads to mitochondrial dysfunction and early death

Oxidative stress is a major driver of the pathophysiology of various cardiovascular diseases; however, there are currently no effective antioxidant therapies. We have identified the mitochondrial transporter ABCB10 as a potential component of a novel cardiac antioxidant system. Hearts from mice with a heterozygous deletion of ABCB10 had decreased cardiac function and increased oxidative stress after ischemia reperfusion; perfusion with an antioxidant corrected the phenotype suggesting the potential of ABCB10 as an antioxidant. To test the role of ABCB10 in cardiomyocytes, we developed a cardiomyocyte-specific ABCB10 homozygous knockout mouse (CM-ABCB10 -/-) using Myh6 cre. Mitochondria were isolated from the hearts of CM-ABCB10 -/- and wild type control mice (WT). Reactive oxygen species (ROS) production was measured using Amplex Ultra Red, and oxygen consumption was measured using Seahorse. CM-ABCB10 -/- mice died earlier than WT cre+ controls. At 10 months of age, only 29% of CM-ABCB10 -/- mice were alive (n=5/17), compared to 86% of wild type cre+ controls (n=13/15, p