Downregulation of respiratory complex I mediates major signalling changes triggered by TOR activation

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F20%3A00523004" target="_blank" >RIV/60077344:_____/20:00523004 - isvavai.cz</a>
Alternative codes found
RIV/60076658:12310/20:43901370
Result on the web
<a href="https://www.nature.com/articles/s41598-020-61244-3.pdf" target="_blank" >https://www.nature.com/articles/s41598-020-61244-3.pdf</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41598-020-61244-3" target="_blank" >10.1038/s41598-020-61244-3</a>

Result language
angličtina
Original language name
Downregulation of respiratory complex I mediates major signalling changes triggered by TOR activation
Original language description
Mitochondrial dysfunctions belong amongst the most common metabolic diseases but the signalling networks that lead to the manifestation of a disease phenotype are often not well understood. We identified the subunits of respiratory complex I, III and IV as mediators of major signalling changes during Drosophila wing disc development. Their downregulation in larval wing disc leads to robust stimulation of TOR activity, which in turn orchestrates a complex downstream signalling network. Specifically, after downregulation of the complex I subunit ND-49 (mammalian NDUFS2), TOR activates JNK to induce cell death and ROS production essential for the stimulation of compensatory apoptosis-induced proliferation within the tissue. Additionally, TOR upregulates Notch and JAK/STAT signalling and it directs glycolytic switch of the target tissue. Our results highlight the central role of TOR signalling in mediating the complex response to mitochondrial respiratory dysfunction and they provide a rationale why the disease symptoms associated with respiratory dysfunctions are often alleviated by mTOR inhibitors.
Czech name
—
Czech description
—

Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10608 - Biochemistry and molecular biology

Project
<a href="/en/project/GA17-17529S" target="_blank" >GA17-17529S: Metabolic stress as regulator of Notch signalling</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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