Consistent with our results, inhibition of neddylation via deletion of NEDD8 or UBA3 in the liver suppressed mitochondrial oxidative phosphorylation and fatty acid oxidation, leading to hepatic steatosis.33 Interestingly, MLN4924 treatment and UBA3 knockdown were shown to enhance basal and maximal oxidative phosphorylation in cancer cell lines,57 suggesting that the effect of neddylation in metabolism could be cell-type dependent. Here, NEDD8 is linked to fatty liver disease.