Role of S-Palmitoylation by ZDHHC13 in Mitochondrial Function and Metabolism in Liver

The study investigated the effects of Zdhhc13 deficiency, a palmitoyltransferase, on liver function and metabolism in mice. It was found that the lack of Zdhhc13 led to abnormal liver function, lipid abnormalities, and hypermetabolism. Using a quantitative approach that combined alkylating resin-assisted capture with mass spectrometry, the researchers identified 2,190 S-palmitoylated peptides from 883 proteins. After normalization, they discovered that 400 S-palmitoylation sites on 254 proteins were down-regulated in Zdhhc13-deficient mice, suggesting these are potential substrates of ZDHHC13. Proteins involved in lipid metabolism and mitochondrial function were particularly affected. Two specific substrates, MCAT and CTNND1, were confirmed, and impaired mitochondrial function was observed in hepatocytes from Zdhhc13-deficient mice and Zdhhc13-knockdown cells. The study concluded that ZDHHC13 plays a crucial role in regulating mitochondrial activity and metabolism in the liver.