Ablation of ceramide synthase 2 causes chronic oxidative stress due to disruption of the mitochondrial respiratory chain

Abstract

Background: Ceramide synthase 2 null mice, which cannot synthesize very-long chain ceramides, display severe hepatopathy. Results: These mice have elevated sphinganine and altered N-acyl chain ceramides that disrupt mitochondrial function by modifying respiratory chain activity. Conclusion: Alteration of mitochondrial sphingolipids results in formation of reaction oxygen species in liver. Significance: Ceramides with defined acyl chains influence oxidative stress signaling pathways.© 2013 by The American Society for Biochemistry and Molecular Biology, Inc.