MCL1 modulates mTORC1 signaling to promote bioenergetics and tumorigenesis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F25%3A00643394" target="_blank" >RIV/61389013:_____/25:00643394 - isvavai.cz</a>
Alternative codes found
RIV/68378050:_____/25:00643394 RIV/00216208:11110/25:10510861 RIV/00216208:11310/25:10510861
Result on the web
<a href="https://www.nature.com/articles/s41467-025-66831-4" target="_blank" >https://www.nature.com/articles/s41467-025-66831-4</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41467-025-66831-4" target="_blank" >10.1038/s41467-025-66831-4</a>
Alternative languages
Result language
angličtina
Original language name
MCL1 modulates mTORC1 signaling to promote bioenergetics and tumorigenesis
Original language description
Myeloid cell leukemia-1 (MCL1) is among the most overexpressed proteins in tumors. MCL1 contributes to tumorigenesis by antagonizing apoptosis. However, apoptosis-unrelated functions are emerging. Screening an array of signaling switches identifies mTORC1 to be modulated by MCL1 but not by the anti-apoptotic Bcl-2 or Bcl-xL. mTORC1 is a central metabolic regulator. MCL1 impacts metabolism via modulating the expression of hexokinase 2 (HK2) in an mTORC1-dependent manner, which ultimately contributes to the tumor-promoting effects of MCL1. MCL1 inhibitors suppress mTORC1 in tumor cells but are associated with cardiotoxicity due to mTORC1 inhibition in the heart. Dietary leucine supplementation rescues mTORC1 signaling in the hearts of humanized Mcl-1 mice and greatly ameliorates the cardiotoxicity of MCL1 inhibitors. Taken together, here we describe tumor-promoting roles for MCL1 in regulating mTORC1 signaling and subsequently in bioenergetics, besides its role in antagonizing apoptosis, identifying MCL1 as a hinge of cell bioenergetics and survival.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10404 - Polymer science
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature Communications
ISSN
2041-1723
e-ISSN
2041-1723
Volume of the periodical
16
Issue of the periodical within the volume
1 December
Country of publishing house
GB - UNITED KINGDOM
Number of pages
20
Pages from-to
10841
UT code for WoS article
001629548500002
EID of the result in the Scopus database
2-s2.0-105023570596