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Article

Target of Rapamycin Complex 1 (TORC1), Protein Kinase A (PKA) and Cytosolic pH Regulate a Transcriptional Circuit for Lipid Droplet Formation

1
Yeast Signalling Networks, i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
2
Yeast Signalling Networks, IBMC—Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugal
3
ICBAS—Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal
4
Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Takeshi Noda
Int. J. Mol. Sci. 2021, 22(16), 9017; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22169017
Received: 5 July 2021 / Revised: 12 August 2021 / Accepted: 19 August 2021 / Published: 20 August 2021
(This article belongs to the Special Issue Yeast Cell Signalling Pathways)
Lipid droplets (LDs) are ubiquitous organelles that fulfill essential roles in response to metabolic cues. The identification of several neutral lipid synthesizing and regulatory protein complexes have propelled significant advance on the mechanisms of LD biogenesis in the endoplasmic reticulum (ER). However, our understanding of signaling networks, especially transcriptional mechanisms, regulating membrane biogenesis is very limited. Here, we show that the nutrient-sensing Target of Rapamycin Complex 1 (TORC1) regulates LD formation at a transcriptional level, by targeting DGA1 expression, in a Sit4-, Mks1-, and Sfp1-dependent manner. We show that cytosolic pH (pHc), co-regulated by the plasma membrane H+-ATPase Pma1 and the vacuolar ATPase (V-ATPase), acts as a second messenger, upstream of protein kinase A (PKA), to adjust the localization and activity of the major transcription factor repressor Opi1, which in turn controls the metabolic switch between phospholipid metabolism and lipid storage. Together, this work delineates hitherto unknown molecular mechanisms that couple nutrient availability and pHc to LD formation through a transcriptional circuit regulated by major signaling transduction pathways. View Full-Text
Keywords: lipid droplet; membrane biogenesis; nutrient; cell signaling; transcription lipid droplet; membrane biogenesis; nutrient; cell signaling; transcription
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MDPI and ACS Style

Teixeira, V.; Martins, T.S.; Prinz, W.A.; Costa, V. Target of Rapamycin Complex 1 (TORC1), Protein Kinase A (PKA) and Cytosolic pH Regulate a Transcriptional Circuit for Lipid Droplet Formation. Int. J. Mol. Sci. 2021, 22, 9017. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22169017

AMA Style

Teixeira V, Martins TS, Prinz WA, Costa V. Target of Rapamycin Complex 1 (TORC1), Protein Kinase A (PKA) and Cytosolic pH Regulate a Transcriptional Circuit for Lipid Droplet Formation. International Journal of Molecular Sciences. 2021; 22(16):9017. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22169017

Chicago/Turabian Style

Teixeira, Vitor, Telma S. Martins, William A. Prinz, and Vítor Costa. 2021. "Target of Rapamycin Complex 1 (TORC1), Protein Kinase A (PKA) and Cytosolic pH Regulate a Transcriptional Circuit for Lipid Droplet Formation" International Journal of Molecular Sciences 22, no. 16: 9017. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22169017

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