Content area
Full Text
Introduction
The lysosome is an important organelle in cells; it has previously been regarded as the ‘garbage disposal’ organelle in cells (1), as it contains >50 soluble acid hydrolases. The lysosome is now regarded as a key subcellular organelle (2), acting to degrade cellular components through initiation by phagocytosis, autophagy and other pathways (3). The characteristic acidic environment (pH 4.5–5.0) of lysosomes provides an optimal environment for lysosomal hydrolase activity, and this contributes to macromolecular degradation (4). If the internal pH changes, the activity of internal hydrolytic enzymes will change, thus affecting the function of the lysosomes. The change of lysosomal function can lead to reactions inside the cell. The lysosomal membrane proteins that are responsible for sustaining membrane integrity and regulating lysosomal function are not completely known. As lysosomal membrane integrity is important for the fate of cells, once it is destroyed by a procedure known as lysosomal membrane permeabilization (LMP), lysosomal content leakage will occur (5). The leakage of lysosomal constituents may be sufficient to trigger cell death (5).
SID1 transmembrane family member 2 (sidt2), a lysosomal membrane protein, has previously been studied (3). Sidt2 is a lysosomal membrane protein. In a previous study, sidt2 was identified as a novel integral lysosomal membrane protein with a molecular weight of 94 kDa (6). Sidt2 functions as an integral protein and is associated with signaling pathways, including the PTEN-induced putative kinase and CUP-5 proteins that regulate lysosomal autophagy and apoptosis (3). The present study utilized a sidt2 deficient mouse model to explore the function and mechanisms of sidt2 action in liver lipid metabolism and changes of LMP.
Materials and methods
Animals
Cre mice mated with sidt2 LoxP-Flox-LoxP−/+ mice to obtain sidt2−/+Cre+/− mice. A total of 100 male and 200 female mice (age, 8–10 weeks; weight, 25–30 g) were purchased from the Shanghai SLAC Laboratory Animal Co., Ltd. (Shanghai, China). Normal male rats can be used for breeding offspring after 8 weeks and females after 10 weeks. The mice were maintained in a controlled temperature (22–25°C) and humidity (50–60%) with a 12 h light/dark cycle and fed a controlled diet and water. The animals had free access to food and water under basic feeding conditions. To prevent the phenotypic effects of...