Hypoxia-reprogramed megamitochondrion contacts and engulfs lysosome to mediate mitochondrial self-digestion.

Mitochondria are the key organelles for sensing oxygen, which is consumed by oxidative phosphorylation to generate ATP. Lysosomes contain hydrolytic enzymes that degrade misfolded proteins and damaged organelles to maintain cellular homeostasis. Mitochondria physically and functionally interact with lysosomes to regulate cellular metabolism. However, the mode and biological functions of mitochondria-lysosome communication remain largely unknown. Here, we show that hypoxia remodels normal tubular mitochondria into megamitochondria by inducing broad inter-mitochondria contacts and subsequent fusion. Importantly, under hypoxia, mitochondria-lysosome contacts are promoted, and certain lysosomes are engulfed by megamitochondria, in a process we term megamitochondria engulfing lysosome (MMEL). Both megamitochondria and mature lysosomes are required for MMEL. Moreover, the STX17-SNAP29-VAMP7 complex contributes to mitochondria-lysosome contacts and MMEL under hypoxia. Intriguingly, MMEL mediates a mode of mitochondrial degradation, which we termed mitochondrial self-digestion (MSD). Moreover, MSD increases mitochondrial ROS production. Our results reveal a mode of crosstalk between mitochondria and lysosomes and uncover an additional pathway for mitochondrial degradation.

Application of Big Data Technology and Visual Neural Network in Emotional Expression Analysis of Oil Painting Theme Creation in Public Environment.

With the progress of science and technology and the arrival of the big data era, people increasingly rely on computers to deal with daily life and related affairs. In recent years, machine learning has become more and more popular and has achieved good results in some fields, which also makes machine learning widely used. Among them, visual neural network technology can more intelligently analyze the emotional expression of oil painting, which is one of the current research hotspots, involving machine vision, pattern recognition, image processing, artificial intelligence, and other fields. However, in the art field, oil painting is still very different from other images. At present, there is no deep learning algorithm to identify the application of emotional expression analysis in oil painting theme creation. This paper will start with the neural network algorithm and combine the big data recognition technology to analyze the emotional expression of the oil painting subject in the public environment and establish the emotional expression analysis model of oil painting creation based on big data and neural network. The experiment shows that the graphics synthesized by this model have high resolution and good definition, but the speed is slow in the process of experimental operation. It takes about one hour to complete a round of image optimization.

LIMP2 gene, evolutionarily conserved regulation by TFE3, relieves lysosomal stress induced by cholesterol.

AIM: Excess cholesterol deposition in lysosomes may result in lysosomal stress and dysfunction. Here, we focus on the role of lysosome membrane protein 2 (LIMP2) in relieving the lysosomal stress caused by excess cholesterol and the mechanism that regulate its expression. MATERIAL AND METHODS: Cholesterol enrichment in lamprey liver tissue was evaluated by RNA transcriptome data analysis, RT-qPCR, H&E, and Oil Red O staining. Gene markers of autophagy and cholesterol synthesis were determined by western blot or RT-qPCR. Lysosomal morphology and pH value was measured by confocal observation or flow cytometry. Dual-Luciferase reporter assay was performed to test the expression regulation relationship. KEY FINDINGS: We report that lamprey limp2 (L-limp2) is evolutionarily highly conserved with human LIMP2 (H-LIMP2). The biological function of L-limp2, consistent with H-LIMP2, includes maintaining lysosomal morphology, modulating autophagy, and aiding cholesterol efflux from lysosomes. Furthermore, we find that both L-limp2 and H-limp2 can restore cholesterol-induced elevation of lysosomal pH and impaired autophagic flux. We demonstrate that lamprey transcription factor binding to IGHM enhancer 3 (L-TFE3) can bind with coordinated lysosomal expression and regulation (CLEAR) elements on the L-limp2 promoter and regulate its expression. Moreover, this regulatory relationship is also available in humans. Taken together, the present study demonstrates that the evolutionarily conserved TFE3-LIMP2 axis may have a protective role against the impaired lysosomal function caused by excess cholesterol. SIGNIFICANCE: The protective effect of TFE3-LIMP2 axis against cholesterol-triggered lysosomal stress may provide a new target for the treatment of diseases caused by excessive cholesterol accumulation in lysosomes.

Bioinformatis analysis reveals possible molecular mechanism of PXR on regulating ulcerative colitis.

Inflammatory bowel disease (IBD) is a chronic, recurrent inflammatory disease of the gastrointestinal (GI) tract. Ulcerative colitis (UC) is a type of IBD. Pregnane X Receptor (PXR) is a member of the nuclear receptor superfamily. In order to deepen understanding and exploration of the molecular mechanism of regulation roles of PXR on UC, biological informatics analysis was performed. First, 878 overlapping differentially expressed genes (DEGs) between UC and normal samples were obtained from the Gene Expression Omnibus (GEO) database (GSE59071 and GSE38713) by using the "limma" R language package. Then WGCNA analysis was performed by 878 DEGs to obtain co-expression modules that were positively and negatively correlated with clinical traits. GSEA analysis of PXR results obtained the signal pathways enriched in the PXR high and low expression group and the active genes of each signal pathway. Then the association of PXR with genes that are both active in high expression group and negatively related to diseases (gene set 1), or both active in low expression group and negatively related to diseases (gene set 2) was analyzed by String database. Finally, carboxylesterase 2 (CES2), ATP binding cassette subfamily G member 2 (ABCG2), phosphoenolpyruvate carboxykinase (PCK1), PPARG coactivator 1 alpha (PPARGC1A), cytochrome P450 family 2 subfamily B member 6 (CYP2B6) from gene set 1 and C-X-C motif chemokine ligand 8 (CXCL8) from gene set 2 were screened out. After the above analysis and reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) verification, we speculated that PXR may exert a protective role on UC by promoting CES2, ABCG2, PCK1, PPARGC1A, CYP2B6 expression and inhibiting CXCL8 expression in their corresponding signal pathway in intestinal tissue.