Mitochondrial respiration supports autophagy to provide stress resistance during quiescence

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F22%3A00557875" target="_blank" >RIV/68378050:_____/22:00557875 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/86652036:_____/22:00557875 RIV/67985823:_____/22:00557875 RIV/00023001:_____/22:00083463 RIV/00216208:11310/22:10456185

Výsledek na webu

<a href="https://www.tandfonline.com/doi/full/10.1080/15548627.2022.2038898" target="_blank" >https://www.tandfonline.com/doi/full/10.1080/15548627.2022.2038898</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/15548627.2022.2038898" target="_blank" >10.1080/15548627.2022.2038898</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Mitochondrial respiration supports autophagy to provide stress resistance during quiescence

Popis výsledku v původním jazyce

Mitochondrial oxidative phosphorylation (OXPHOS) generates ATP, but OXPHOS also supports biosynthesis during proliferation. In contrast, the role of OXPHOS during quiescence, beyond ATP production, is not well understood. Using mouse models of inducible OXPHOS deficiency in all cell types or specifically in the vascular endothelium that negligibly relies on OXPHOS-derived ATP, we show that selectively during quiescence OXPHOS provides oxidative stress resistance by supporting macroautophagy/autophagy. Mechanistically, OXPHOS constitutively generates low levels of endogenous ROS that induce autophagy via attenuation of ATG4B activity, which provides protection from ROS insult. Physiologically, the OXPHOS-autophagy system (i) protects healthy tissue from toxicity of ROS-based anticancer therapy, and (ii) provides ROS resistance in the endothelium, ameliorating systemic LPS-induced inflammation as well as inflammatory bowel disease. Hence, cells acquired mitochondria during evolution to profit from oxidative metabolism, but also built in an autophagy-based ROS-induced protective mechanism to guard against oxidative stress associated with OXPHOS function during quiescence.

Název v anglickém jazyce

Mitochondrial respiration supports autophagy to provide stress resistance during quiescence

Popis výsledku anglicky

Mitochondrial oxidative phosphorylation (OXPHOS) generates ATP, but OXPHOS also supports biosynthesis during proliferation. In contrast, the role of OXPHOS during quiescence, beyond ATP production, is not well understood. Using mouse models of inducible OXPHOS deficiency in all cell types or specifically in the vascular endothelium that negligibly relies on OXPHOS-derived ATP, we show that selectively during quiescence OXPHOS provides oxidative stress resistance by supporting macroautophagy/autophagy. Mechanistically, OXPHOS constitutively generates low levels of endogenous ROS that induce autophagy via attenuation of ATG4B activity, which provides protection from ROS insult. Physiologically, the OXPHOS-autophagy system (i) protects healthy tissue from toxicity of ROS-based anticancer therapy, and (ii) provides ROS resistance in the endothelium, ameliorating systemic LPS-induced inflammation as well as inflammatory bowel disease. Hence, cells acquired mitochondria during evolution to profit from oxidative metabolism, but also built in an autophagy-based ROS-induced protective mechanism to guard against oxidative stress associated with OXPHOS function during quiescence.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell 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

2022

Kód důvěrnosti údajů

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

Název periodika

Autophagy

ISSN

1554-8627

e-ISSN

1554-8635

Svazek periodika

18

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

19

Strana od-do

2409-2426

Kód UT WoS článku

000766134900001

EID výsledku v databázi Scopus

2-s2.0-85126384039