Alternative assembly of respiratory complex II connects energy stress to metabolic checkpoints

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12310%2F18%3A43897308" target="_blank" >RIV/60076658:12310/18:43897308 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/86652036:_____/18:00492386 RIV/68378050:_____/18:00492386

Výsledek na webu

<a href="https://www.nature.com/articles/s41467-018-04603-z#author-information" target="_blank" >https://www.nature.com/articles/s41467-018-04603-z#author-information</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-018-04603-z" target="_blank" >10.1038/s41467-018-04603-z</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Alternative assembly of respiratory complex II connects energy stress to metabolic checkpoints

Popis výsledku v původním jazyce

Cell growth and survival depend on a delicate balance between energy production and synthesis of metabolites. Here, we provide evidence that an alternative mitochondrial complex II (CII) assembly, designated as CIIlow, serves as a checkpoint for metabolite biosynthesis under bioenergetic stress, with cells suppressing their energy utilization by modulating DNA synthesis and cell cycle progression. Depletion of CIIlow leads to an imbalance in energy utilization and metabolite synthesis, as evidenced by recovery of the de novo pyrimidine pathway and unlocking cell cycle arrest from the S-phase. In vitro experiments are further corroborated by analysis of paraganglioma tissues from patients with sporadic, SDHA and SDHB mutations. These findings suggest that CIIlow is a core complex inside mitochondria that provides homeostatic control of cellular metabolism depending on the availability of energy.

Název v anglickém jazyce

Alternative assembly of respiratory complex II connects energy stress to metabolic checkpoints

Popis výsledku anglicky

Cell growth and survival depend on a delicate balance between energy production and synthesis of metabolites. Here, we provide evidence that an alternative mitochondrial complex II (CII) assembly, designated as CIIlow, serves as a checkpoint for metabolite biosynthesis under bioenergetic stress, with cells suppressing their energy utilization by modulating DNA synthesis and cell cycle progression. Depletion of CIIlow leads to an imbalance in energy utilization and metabolite synthesis, as evidenced by recovery of the de novo pyrimidine pathway and unlocking cell cycle arrest from the S-phase. In vitro experiments are further corroborated by analysis of paraganglioma tissues from patients with sporadic, SDHA and SDHB mutations. These findings suggest that CIIlow is a core complex inside mitochondria that provides homeostatic control of cellular metabolism depending on the availability of energy.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Nature Communications

ISSN

2041-1723

e-ISSN

—

Svazek periodika

9

Číslo periodika v rámci svazku

JUN 7 2018

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

17

Strana od-do

—

Kód UT WoS článku

000434379800018

EID výsledku v databázi Scopus

2-s2.0-85048232435