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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/60076658:12310/20:43901370

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GA17-17529S" target="_blank" >GA17-17529S: Metabolický stres jako regulátor signalizace přes receptor Notch</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Scientific Reports

ISSN

2045-2322

e-ISSN

—

Svazek periodika

10

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

13

Strana od-do

4401

Kód UT WoS článku

000563372900003

EID výsledku v databázi Scopus

2-s2.0-85081607911