Mitochondrial GCN5L1 regulates glutaminase acetylation and hepatocellular carcinoma.

BACKGROUND: Glutaminolysis is a critical metabolic process that promotes cancer cell proliferation, including hepatocellular carcinoma (HCC). Delineating the molecular control of glutaminolysis could identify novel targets to ameliorate this oncogenic metabolic pathway. Here, we evaluated the role of general control of amino acid synthesis 5 like 1 (GCN5L1), a regulator of mitochondrial protein acetylation, in modulating the acetylation and activity of glutaminase to regulate HCC development. METHODS: Cell proliferation was determined by MTT, 2D and soft agar clone formation assays and orthotopic tumour assays in nude mice. GLS1/2 acetylation and activities were measured in cells and tumours to analyse the correlation with GCN5L1 expression and mTORC1 activation. RESULTS: Hepatic GCN5L1 ablation in mice markedly increased diethylnitrosamine (DEN)-induced HCC, and conversely, the transduction of mitochondrial-restricted GCN5L1 protected wild-type mice against HCC progression in response to DEN and carbon tetrachloride (CCl4 ) exposure. GCN5L1-depleted HepG2 hepatocytes enhanced tumour growth in athymic nude mice. Mechanistically, GCN5L1 depletion promoted cell proliferation through mTORC1 activation. Interestingly, liver-enriched glutaminase 2 (GLS2) appears to play a greater role than ubiquitous and canonical tumour-enriched glutaminase 1 (GLS1) in promoting murine HCC. Concurrently, GCN5L1 promotes acetylation and inactivation of both isoforms and increases enzyme oligomerisation. In human HCC tumours compared to adjacent tissue, there were variable levels of mTORC1 activation, GCN5L1 levels and glutaminase activity. Interestingly, the levels of GCN5L1 inversely correlated with mTORC1 activity and glutaminase activity in these tumours. CONCLUSIONS: Our study identified that glutaminase activity, rather than GLS1 or GLS2 expression, is the key factor in HCC development that activates mTORC1 and promotes HCC. In the Kaplan-Meier analysis of liver cancer, we found that HCC patients with high GCN5L1 expression survived longer than those with low GCN5L1 expression. Collectively, GCN5L1 functions as a tumour regulator by modulating glutaminase acetylation and activity in the development of HCC.

Triboelectric charging of melt-blown nonwoven filters with high filtration efficiency.

As a novel technology to convert low-frequency energy into electric power, the triboelectric nanogenerator is a hot research topic recently. However, the nature of charge carriers and their transfer mechanisms still remain poorly understood, especially for the cases of liquid-solid triboelectric nanogenerator. In this paper, charges produced by a triboelectric charging process were designed to provide melt-blown nonwoven fabrics with high filtration efficiency by making full use of the electrostatic attraction filtration mechanism. Influences of water conductivity and drying temperature on the filtration efficiency of melt-blown nonwoven fabrics were investigated. And the corresponding properties such as the surface charge potential and charge stability were analyzed by using the electrostatic voltmeter, bio atomic force microscope and thermally stimulated discharge technique. In addition, metal and inorganic elements in the masterbatch and water before and after triboelectric charging were measured in order to uncover the charge transfer mechanism. Melt-blown nonwoven fabrics with filtration efficiency as high as 96.8% was obtained through the triboelectric charging treatment by using water with the conductivity as low as 1.1 µS/cm for the first time. Negative and positive surface charge density appeared randomly on both sides of melt-blown nonwoven fabrics after the triboelectric charging treatment from the bio atomic force microscope measurement while only one kind of surface charge density can be achieved in the research of TENG, that is, negative or positive. It seems there are both electron and ion transfers during the triboelectric charging process and electron transfer seems to have more important contribution for the generation of charges.