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

Area of Science:

• Cellular Biology
• Metabolism
• Mitochondrial Function

Background:

• Fasting profoundly impacts cellular energy production.
• Mammalian target of rapamycin (mTOR) is a key regulator of mitochondrial biogenesis and function.
• Protein arginine methyltransferase 1 (PRMT1) influences mitochondrial activity.

Purpose of the Study:

• To investigate the role of PRMT1 in regulating mitochondrial function during fasting.
• To elucidate the molecular mechanisms linking fasting, mTOR signaling, and PRMT1 expression.
• To assess the impact of fasting on mitochondrial mass and cellular energy homeostasis.

Main Methods:

• Assessed mTOR signaling and mitochondrial mass in LO2 cells and C57BL/6J mice.
• Utilized quantitative PCR, Western blotting, immunofluorescence, and MitoTracker staining.
• Investigated gene and protein expression, protein interactions, and mitochondrial content.

Main Results:

• Fasting (48h) significantly reduced mTOR, PRMT1 expression, and mitochondrial mass in vitro and in vivo.
• Fasting downregulated miR-21 and upregulated PTEN, leading to decreased mTOR expression.
• Inhibition of mTOR reduced PRMT1 expression, which subsequently decreased peroxisome proliferator-activated receptor (PPAR)-γ and mitochondrial mass.

Conclusions:

• Fasting-induced downregulation of miR-21 and upregulation of PTEN inhibit mTOR signaling, p-STAT1, PRMT1, and mitochondrial mass.
• mTOR and PRMT1 play critical roles in managing cellular energy supply during fasting.
• Insulin supplementation counteracted the effects of fasting on these cellular parameters.