ALCAT1 Overexpression Affects Supercomplex Formation and Increases ROS in Respiring Mitochondria

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F19%3A43919452" target="_blank" >RIV/00216208:11120/19:43919452 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1155/2019/9186469" target="_blank" >https://doi.org/10.1155/2019/9186469</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1155/2019/9186469" target="_blank" >10.1155/2019/9186469</a>

Jazyk výsledku

angličtina

Název v původním jazyce

ALCAT1 Overexpression Affects Supercomplex Formation and Increases ROS in Respiring Mitochondria

Popis výsledku v původním jazyce

Cardiolipin (CL) is a multifunctional dimeric phospholipid that physically interacts with electron transport chain complexes I, III, and IV, and ATP synthase (complex V). The enzyme ALCAT1 catalyzes the conversion of cardiolipin by incorporating polyunsaturated fatty acids into cardiolipin. The resulting CL species are said to be more susceptible to oxidative damage. This is thought to negatively affect the interaction of cardiolipin and electron transport chain complexes, leading to increased ROS production and mitochondrial dysfunction. Furthermore, it is discussed that ALCAT1 itself is upregulated due to oxidative stress. Here, we investigated the effects of overexpression of ALCAT1 under different metabolic conditions. ALCAT1 is located at the ER and mitochondria, probably at contact sites. We found that respiration stimulated by galactose supply promoted supercomplex assembly but also led to increased mitochondrial ROS levels. Endogeneous ALCAT1 protein expression levels showed a fairly high variability. Artificially induced ALCAT1 overexpression reduced supercomplex formation, further promoted ROS production, and prevented upregulation of coupled respiration. Taken together, our data suggest that the amount of the CL conversion enzyme ALCAT1 is critical for coupling mitochondrial respiration and metabolic plasticity.

Název v anglickém jazyce

ALCAT1 Overexpression Affects Supercomplex Formation and Increases ROS in Respiring Mitochondria

Popis výsledku anglicky

Cardiolipin (CL) is a multifunctional dimeric phospholipid that physically interacts with electron transport chain complexes I, III, and IV, and ATP synthase (complex V). The enzyme ALCAT1 catalyzes the conversion of cardiolipin by incorporating polyunsaturated fatty acids into cardiolipin. The resulting CL species are said to be more susceptible to oxidative damage. This is thought to negatively affect the interaction of cardiolipin and electron transport chain complexes, leading to increased ROS production and mitochondrial dysfunction. Furthermore, it is discussed that ALCAT1 itself is upregulated due to oxidative stress. Here, we investigated the effects of overexpression of ALCAT1 under different metabolic conditions. ALCAT1 is located at the ER and mitochondria, probably at contact sites. We found that respiration stimulated by galactose supply promoted supercomplex assembly but also led to increased mitochondrial ROS levels. Endogeneous ALCAT1 protein expression levels showed a fairly high variability. Artificially induced ALCAT1 overexpression reduced supercomplex formation, further promoted ROS production, and prevented upregulation of coupled respiration. Taken together, our data suggest that the amount of the CL conversion enzyme ALCAT1 is critical for coupling mitochondrial respiration and metabolic plasticity.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

—

Návaznosti

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Oxidative Medicine and Cellular Longevity

ISSN

1942-0900

e-ISSN

—

Svazek periodika

2019

Číslo periodika v rámci svazku

December

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

"Article 9186469"

Kód UT WoS článku

000503780800006

EID výsledku v databázi Scopus

2-s2.0-85076926533