mTOR regulates PRMT1 expression and mitochondrial mass through STAT1 phosphorylation in hepatic cell

Fasting changes mitochondrial function, and mTOR acts as a major regulator of mitochondrial energy production ensuring the survival under reduced supply of nutrition. This study assessed the role of protein arginine methyltransferase 1 (PRMT1), which regulates mitochondrial function, in the context of fasting. The effect of fasting on mTOR signaling and mTOR-regulated mitochondrial mass was assessed in LO2 cells (in vitro) and C57BL/6J mice (in vivo). Biochemical parameters of fasting were determined in blood samples of mice. PRMT1 expression was investigated by transfecting LO2 cells with an expression vector. Gene expression was determined by real-time quantitative PCR, protein interaction by chromatin immunoprecipitation, protein expression by Western blotting and immunofluorescence microscopy, and the mitochondrial mass by MitoTracker staining. After 48 h of fasting, mTOR and PRMT1 expression, as well as mitochondrial mass, were significantly reduced in LO2 cells, and in liver tissue sections. Fasting downregulated the expression of miR-21 and upregulated the expression of its target phosphatase and tensin homolog (PTEN), which was responsible for reduced mTOR expression. Inhibition of mTOR reduced phosphorylation of STAT1, and thereby PRMT1 expression in LO2 cells. Low PRMT1 down-regulated the expression of peroxisome proliferator-activated receptor (PPAR)-γ and thereby decreased mitochondrial mass. Supplementation of insulin contracted the effect of fasting on all mentioned parameters. Fasting downregulates miR-21 and increases its target PTEN, thereby inhibiting mTOR signaling, p-STAT1, PRMT1, and mitochondrial mass. These findings highlight the role of mTOR and PRMT1 in the regulation of cellular energy availability. The study demonstrated that the molecular mechanism of the mTOR/STAT1/PRMT1 signal axis regulates mitochondrial mass. miR-21 targets PTEN to suppress mTOR expression, which regulates PRMT1 through the phosphorylation of STAT1. PRMT1 participates in regulating the mitochondrial mass through PPARγ. Therefore, mTOR and PRMT1 are attractive targets for regulating mitochondrial mass and signaling pathways associated with energy utilization. [Display omitted] •Fasting downregulates miR-21 and increases its target PTEN, thereby inhibiting mTOR signaling.•mTOR regulates PRMT1 through the phosphorylation of STAT1.•PRMT1 participates in regulating the mitochondrial mass through PPARγ.