Molecular mechanism of metabolic disorder caused by mysterious proteins

According to a study published in the journal Nature Structural & molecular biology by researchers from the University of South Carolina, the response of cells to misfolded proteins may be the cause of metabolic disorders rather than the result In this study, the authors identified a previously poorly reported molecule that triggers the effects of metabolic disorders (photo source: Dr Feng Hong of the Medical University of South Carolina.) These studies have shown that protein folding can cause specific metabolic disorders When improperly folded molecules enter the cell, a phenomenon called "unfolded protein response" will be triggered in the endoplasmic reticulum It is well known that endoplasmic reticulum is an important organelle structure for protein synthesis and modification One protein, GRP78, is the core component of UPR When the unfolded or misfolded protein meets GRP78, the latter will dissociate from its original linked protein and activate UPR reaction Furthermore, UPR will refold or degrade these molecules to ensure that they will not enter other parts to perform their functions However, when there are too many misfolded proteins in cells, UPR will be overloaded When a large number of cells are overloaded, organs will be threatened by diseases In this study, the authors found a mechanism by which molecules called cnpy2 influence this process Cnpy2 is a kind of protein existing in Er, but its function has not been known before In addition, when fed with a drug known to cause UPR, tunicamycin, the wild-type mice can produce liver pressure and activation of perk, while the mutant mice will not be affected This result suggests that cnpy2 may be involved in UPR regulation After that, the author fed the mice a high-fat diet and found that the metabolic homeostasis of the mutant mice could be well maintained, while the control mice would have similar symptoms of nonalcoholic fatty liver Based on these phenomena, the researchers believe that cnpy2 plays an important role in the occurrence of liver diseases induced by high-fat diet, and that cnpy2 may be the effect of interaction with perk, one of the UPR sensing elements.