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The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.

Genome-wide CRISPR screens reveal multitiered mechanisms through which mTORC1 senses mitochondrial dysfunction

Condon, Kendall J., Orozco, Jose M., Adelmann, Charles H., Spinelli, Jessica B., van der Helm, Pim W., Roberts, Justin M., Kunchok, Tenzin, Sabatini, David M.·2021·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.2022120118

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Abstract

Significance: The mTORC1 eukaryotic cell growth regulator dynamically responds to changes in environmental nutrient levels. While many upstream regulators are known to modulate mTORC1 activity, the full complement of these is unknown. Here, using a genome-wide FACS-based CRISPR-Cas9 screen, we identify almost all known positive regulators of mTORC1 as well as many others. The results of our screens highlighted the importance of mitochondrial health in the regulation of mTORC1, which led us to investigate how mitochondrial stress impinges on mTORC1 signaling. Ultimately, we found that two kinases, AMPK and HRI, together signal mitochondrial distress to mTORC1. Furthermore, full inhibition of mTORC1 by mitochondrial stress requires the ATF4-dependent up-regulation of two mTORC1 pathway inhibitors, Sestrin2 and Redd1.

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  • ATF4 may act as a brake on mTORC1 in response to mitochondrial distress, with ATF4 inhibiting mTORC1 activity via upregulation of Sestrin2 and Redd1.

    “ATF4 instead may act as a break on mTORC1 in response to mitochondrial distress, with ATF4 inhibiting mTORC1 activity via upregulation of the mTORC1 inhibitors Sestrin2 and Redd1 60.”

    From Targeting the biology of aging with mTOR inhibitors (2023) · cites this paper as [60]

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Research works printed but not linked: 46

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Metadata

Authors
Condon, K. J., Orozco, J. M., Adelmann, C. H., Spinelli, J. B., van der Helm, P. W., Roberts, J. M., Kunchok, T., & Sabatini, D. M.
Affiliations
Whitehead Institute for Biomedical Research, Cambridge, MA 02142;
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2021-01-22
Volume
118
Issue
4
ISSN
  • 0027-8424
  • 1091-6490
DOI
10.1073/pnas.2022120118
Cited by
137
References
15
Language
en
Licence
www.pnas.org/site/aboutpnas/licenses.xhtml (vor, 181 d)
Funders
  • HHS | National Institutes of Health (R01 CA103866, R01 CA129105, R01 AI047389, F30CA210373, F31CA228241-01, K00CA234839, F31CA232355)
  • National Science Foundation (2016197106)

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