Rheb and mammalian target of rapamycin in mitochondrial homoeostasis
Open Access
- 1 December 2013
- journal article
- review article
- Published by The Royal Society in Open Biology
- Vol. 3 (12), 130185
- https://doi.org/10.1098/rsob.130185
Abstract
Mitochondrial dysfunction has been associated with various diseases, such as cancer, myopathies, neurodegeneration and obesity. Mitochondrial homoeostasis is achieved by mechanisms that adapt the number of mitochondria to that required for energy production and for the supply of metabolic intermediates necessary to sustain cell growth. Simultaneously, mitochondrial quality control mechanisms are in place to remove malfunctioning mitochondria. In the cytoplasm, the protein complex mTORC1 couples growth-promoting signals with anabolic processes, in which mitochondria play an essential role. Here, we review the involvement of mTORC1 and Rheb in mitochondrial homoeostasis. The regulatory processes downstream of mTORC1 affect the glycolytic flux and the rate of mitophagy, and include regulation of the transcription factors HIF1α and YY1/PGC-1α. We also discuss how mitochondrial function feeds back on mTORC1 via reactive oxygen species signalling to adapt metabolic processes, and highlight how mTORC1 signalling is integrated with the unfolded protein response in mitochondria, which in Caenorhabditis elegans is mediated via transcription factors such as DVE-1/UBL-5 and ATFS-1.Keywords
This publication has 120 references indexed in Scilit:
- Ragulator Is a GEF for the Rag GTPases that Signal Amino Acid Levels to mTORC1Cell, 2012
- Feedback on Fat: p62-mTORC1-Autophagy ConnectionsCell, 2011
- Mitochondrial stress: A bridge between mitochondrial dysfunction and metabolic diseases?Cellular Signalling, 2011
- Pyruvate Kinase M2 Is a PHD3-Stimulated Coactivator for Hypoxia-Inducible Factor 1Cell, 2011
- Activation of a Metabolic Gene Regulatory Network Downstream of mTOR Complex 1Molecular Cell, 2010
- Glucose Addiction of TSC Null Cells Is Caused by Failed mTORC1-Dependent Balancing of Metabolic Demand with SupplyMolecular Cell, 2010
- Ragulator-Rag Complex Targets mTORC1 to the Lysosomal Surface and Is Necessary for Its Activation by Amino AcidsCell, 2010
- 4E-BP Extends Lifespan upon Dietary Restriction by Enhancing Mitochondrial Activity in DrosophilaCell, 2009
- Hypoxic activation of AMPK is dependent on mitochondrial ROS but independent of an increase in AMP/ATP ratioFree Radical Biology & Medicine, 2009
- Brick by brick: metabolism and tumor cell growthCurrent Opinion in Genetics & Development, 2008