Increased ceramide content in mitochondria of Cert^gt/gt compromises mitochondrial function. (A) CERT deficiency and lack of ceramide transfer out of the ER causes increased ceramide levels in the mitochondria. (B) The cytochrome c oxidase activity, the terminal reaction in ATP generation, was decreased by more than half in the mutant mitochondria (n = 3; error bars are very small and indicate the standard error of the mean). +/+, wild type; −/−, homozygous mutant.