The histidine triad nucleotide‐binding protein 2 (HINT‐2) positively regulates hepatocellular energy metabolism

What is it about?

Fatty liver is now the most common liver disease worldwide. We have discovered one protein called HINT-2 (Histidine Triad Nucleotide Binding Protein-2) that resides in the mitochondria of liver cells. When this protein is knocked out in mouse liver cells, a fatty liver develops. We studied the function of this HINT-2 protein in a mouse model to gain a better understanding of all the factors that can trigger fatty liver in humans. We found that HINT-2 helps the mitochondria respire and supply energy for liver cell functions. When HINT-2 protein is absent, cells respire poorly and produce less energy. They also lose their reserve capacity, which is normally tapped into when energy demands increase. Conversely, when HINT-2 protein is present at high levels, cells increase their respiration and augment their reserve capacity so that they are able to withstand metabolic stress. We found that the HINT-2 protein binds to components within the mitochondria: an important lipid and chaperone protein that together anchor the respiration system. Therefore, without HINT-2 protein, liver cells cannot meet their energy demands and will accumulate fat. This work identifies a new regulator of fatty liver.

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