mTORC1 Controls Mitochondrial Activity and Biogenesis through 4E-BP-Dependent Translational Regulation (Cell Metabolism)

Paper link: mTORC1 Controls Mitochondrial Activity and Biogenesis through 4E-BP-Dependent Translational Regulation (Cell Metabolism)

Mammalian target of rapamycin (mTOR) is a protein responsible for integrating cellular signals related to energy generation and consumption - in essence it is integral to balancing the cellular energy budget. It forms two complexes, known as mTORC1 and mTORC2, and the authors find that mTORC1 stimulates both mitochondrial biogenesis and activity by phosphorylation of 4E-BP proteins. These function by binding to mRNAs and bringing them to ribosomes, and are essential for the translation of most proteins.

The authors find that when mTOR is inhibited the expression of a subset of mitochondrial proteins is repressed and the level of mitochondrial respiration decreases, lowering the cellular ATP concentration. Reduced levels of Raptor (a protein necessary for mTORC1 formation) led to decreased mitochondrial activity and copy number, whereas a reduction in Rictor (which is necessary for mTORC2) did not have these effects, and led to an increase in cellular ATP turnover, indicating that mTORC1 exerts most of the control on mitochondrial biogenesis.

This indicates that mTORC1 plays an important role in regulating nuclear-encoded mitochondrial protein synthesis to allow mitochondrial activity to match the energy demands of the cell.