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.
Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Balpha
A rapamycin-sensitive pathway down-regulates insulin signaling via phosphorylation and proteasomal degradation of insulin receptor substrate-1
FKBP12-rapamycin-associated protein associates with mitochondria and senses osmotic stress via mitochondrial dysfunction
mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery
AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation
Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase activation in a rapamycin- and farnesylation-dependent manner.
Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb
Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase
Hexokinase-mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax and Bak
The stress-inducted proteins RTP801 and RTP801L are negative regulators of the mammalian target of rapamycin pathway.
Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis
Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase
Ubiquitin-like protein 5 positively regulates chaperone gene expression in the mitochondrial unfolded protein response
The mammalian target of rapamycin (mTOR) pathway regulates mitochondrial oxygen consumption and oxidative capacity
NRF2-dependent glutamate-L-cysteine ligase catalytic subunit expression mediates insulin protection against hyperglycemia- induced brain endothelial cell apoptosis
Cytokine stimulation promotes glucose uptake via phosphatidylinositol-3 kinase/Akt regulation of Glut1 activity and trafficking
Hypoxia-inducible factor 1alpha is regulated by the mammalian target of rapamycin (mTOR) via an mTOR signaling motif
S6 kinase deletion suppresses muscle growth adaptations to nutrient availability by activating AMP kinase
p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy
Discovery of genes activated by the mitochondrial unfolded protein response (mtUPR) and cognate promoter elements
Bnip3 mediates the hypoxia-induced inhibition on mammalian target of rapamycin by interacting with Rheb
Hypoxia regulates TSC1/2-mTOR signaling and tumor suppression through REDD1-mediated 14-3-3 shuttling
Oncogenic MAPK signaling stimulates mTORC1 activity by promoting RSK-mediated raptor phosphorylation
Skeletal muscle-specific ablation of raptor, but not of rictor, causes metabolic changes and results in muscle dystrophy
Hypoxic activation of AMPK is dependent on mitochondrial ROS but independent of an increase in AMP/ATP ratio
Glycolytic flux signals to mTOR through glyceraldehyde-3-phosphate dehydrogenase-mediated regulation of Rheb
The matrix peptide exporter HAF-1 signals a mitochondrial UPR by activating the transcription factor ZC376.7 in C. elegans
Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids
Disease-causing mutations in parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy
Glucose addiction of TSC null cells is caused by failed mTORC1-dependent balancing of metabolic demand with supply
Nix is critical to two distinct phases of mitophagy, reactive oxygen species-mediated autophagy induction and Parkin-ubiquitin-p62-mediated mitochondrial priming.
Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy
Nanoscale mapping and affinity constant measurement of signal-transducing proteins by atomic force microscopy
Redox regulates mammalian target of rapamycin complex 1 (mTORC1) activity by modulating the TSC1/TSC2-Rheb GTPase pathway.
Nucleus-encoded regulators of mitochondrial function: integration of respiratory chain expression, nutrient sensing and metabolic stress
Mitophagy plays an essential role in reducing mitochondrial production of reactive oxygen species and mutation of mitochondrial DNA by maintaining mitochondrial quantity and quality in yeast.
Tyrosine phosphorylation of mitochondrial pyruvate dehydrogenase kinase 1 is important for cancer metabolism
Defective mitochondrial morphology and bioenergetic function in mice lacking the transcription factor Yin Yang 1 in skeletal muscle
Starvation-induced autophagy is regulated by mitochondrial reactive oxygen species leading to AMPK activation
The NAD(+)/Sirtuin Pathway Modulates Longevity through Activation of Mitochondrial UPR and FOXO Signaling
Loss of HMG-CoA reductase in C. elegans causes defects in protein prenylation and muscle mitochondria
Mitochondrial EF4 links respiratory dysfunction and cytoplasmic translation in Caenorhabditis elegans
Chemical genomics approach to identify genes associated with sensitivity to rapamycin in the fission yeast Schizosaccharomyces pombe
mTOR inhibition attenuates glucose deprivation-induced death in photoreceptors via suppressing a mitochondria-dependent apoptotic pathway
The SEACIT complex is involved in the maintenance of vacuole-mitochondria contact sites and controls mitophagy
A Drosophila genetic screen for suppressors of S6kinase-dependent growth identifies the F-box subunit Archipelago/FBXW7
SREBP-regulated adipocyte lipogenesis is dependent on substrate availability and redox modulation of mTORC1
Hyperactivation of mammalian target of rapamycin complex 1 by HIV-1 is necessary for virion production and latent viral reactivation
Rheb1 protects against cisplatin-induced tubular cell death and acute kidney injury via maintaining mitochondrial homeostasis.
TSC2 Deficiency Unmasks a Novel Necrosis Pathway That Is Suppressed by the RIP1/RIP3/MLKL Signaling Cascade
Differential metabolic sensitivity of insulin-like-response- and TORC1-dependent overgrowth in Drosophila fat cells.
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