RUNDC1 inhibits autolysosome formation and survival of zebrafish via clasping ATG14-STX17-SNAP29 complex.

Autophagy serves as a pro-survival mechanism for a cell or a whole organism to cope with nutrient stress. Our understanding of the molecular regulation of this fusion event remains incomplete. Here, we identified RUNDC1 as a novel ATG14-interacting protein, which is highly conserved across vertebrates, including zebrafish and humans. By gain and loss of function studies, we demonstrate that RUNDC1 negatively modulates autophagy by blocking fusion between autophagosomes and lysosomes via inhibiting the assembly of the STX17-SNAP29-VAMP8 complex both in human cells and the zebrafish model. Moreover, RUNDC1 clasps the ATG14-STX17-SNAP29 complex via stimulating ATG14 homo-oligomerization to inhibit ATG14 dissociation. This also prevents VAMP8 from binding to STX17-SNAP29. We further identified that phosphorylation of RUNDC1 Ser379 is crucial to inhibit the assembly of the STX17-SNAP29-VAMP8 complex via promoting ATG14 homo-oligomerization. In line with our findings, RunDC1 is crucial for zebrafish in their response to nutrient-deficient conditions. Taken together, our findings demonstrate that RUNDC1 is a negative regulator of autophagy that restricts autophagosome fusion with lysosomes by clasping the ATG14-STX17-SNAP29 complex to hinder VAMP8 binding.

The role of N-glycosylation modification in the pathogenesis of liver cancer.

N-glycosylation is one of the most common types of protein modifications and it plays a vital role in normal physiological processes. However, aberrant N-glycan modifications are closely associated with the pathogenesis of diverse diseases, including processes such as malignant transformation and tumor progression. It is known that the N-glycan conformation of the associated glycoproteins is altered during different stages of hepatocarcinogenesis. Characterizing the heterogeneity and biological functions of glycans in liver cancer patients will facilitate a deeper understanding of the molecular mechanisms of liver injury and hepatocarcinogenesis. In this article, we review the role of N-glycosylation in hepatocarcinogenesis, focusing on epithelial-mesenchymal transition, extracellular matrix changes, and tumor microenvironment formation. We highlight the role of N-glycosylation in the pathogenesis of liver cancer and its potential applications in the treatment or diagnosis of liver cancer.

1H-NMR metabolomics analysis of nutritional components from two kinds of freshwater fish brain extracts.

There are a number of bioactive compounds in freshwater fish brains, and their functional roles have not been clearly elucidated. NMR-based metabolic profiling could enable rapid characterization of the nutritional composition a fish's brain. Here, two kinds of freshwater fish brains were investigated, crucian carp and yellow catfish. A 1H-NMR based metabolomic approach was used to illustrate the nutritional components of these two kinds of brain. At first, the microwave method was utilized to cease the activity of the enzymes in the brain, and the chemicals were extracted for NMR analysis. These two kinds of brain had significant differences in metabolic patterns, and the chemical compositions of the yellow catfish brain were similar to those of rodent and human brains. Furthermore, most of the different metabolites were significantly higher in the yellow catfish, except for acetamide. This study could provide comprehensive information regarding the utilization of fish heads during processing of fish and dietary nutrition guidance.