Alteration of structure and function of ATP synthase and cytochrome c oxidase by lack of F-o-a and Cox3 subunits caused by mitochondrial DNA 9205delTA mutation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F15%3A00448192" target="_blank" >RIV/67985823:_____/15:00448192 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1042/BJ20141462" target="_blank" >http://dx.doi.org/10.1042/BJ20141462</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1042/BJ20141462" target="_blank" >10.1042/BJ20141462</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Alteration of structure and function of ATP synthase and cytochrome c oxidase by lack of F-o-a and Cox3 subunits caused by mitochondrial DNA 9205delTA mutation

Popis výsledku v původním jazyce

Mutations in the MT-ATP6 gene are frequent causes of severe mitochondrial disorders. To gain more insight into the pathogenic mechanism of mtDNA 9205delTA mutation in MT-ATP6 gene, we prepared cybrids with mutation load ranging between 52 and 99% and investigated changes in the structure and function of ATP synthase and the COX. We found that 9205delTA mutation strongly reduced the levels of both Fo-a and Cox3 proteins. Lack of Fo-a alters the structure but not the content of ATP synthase, which assembles into a labile, similar to 60 kDa smaller, complex retaining ATP hydrolytic activity but which is unable to synthesize ATP. In contrast, lack of Cox3 limits the biosynthesis of COX but does not alter the structure of the enzyme. Consequently, the diminished mitochondrial content of COX and non-functional ATP synthase prevent most mitochondrial ATP production. The biochemical effects caused by the 9205delTA microdeletion displayed a pronounced threshold effect above sililar to 90%mutati

Název v anglickém jazyce

Alteration of structure and function of ATP synthase and cytochrome c oxidase by lack of F-o-a and Cox3 subunits caused by mitochondrial DNA 9205delTA mutation

Popis výsledku anglicky

Mutations in the MT-ATP6 gene are frequent causes of severe mitochondrial disorders. To gain more insight into the pathogenic mechanism of mtDNA 9205delTA mutation in MT-ATP6 gene, we prepared cybrids with mutation load ranging between 52 and 99% and investigated changes in the structure and function of ATP synthase and the COX. We found that 9205delTA mutation strongly reduced the levels of both Fo-a and Cox3 proteins. Lack of Fo-a alters the structure but not the content of ATP synthase, which assembles into a labile, similar to 60 kDa smaller, complex retaining ATP hydrolytic activity but which is unable to synthesize ATP. In contrast, lack of Cox3 limits the biosynthesis of COX but does not alter the structure of the enzyme. Consequently, the diminished mitochondrial content of COX and non-functional ATP synthase prevent most mitochondrial ATP production. The biochemical effects caused by the 9205delTA microdeletion displayed a pronounced threshold effect above sililar to 90%mutati

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

—

Projekt

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

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2015

Kód důvěrnosti údajů

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

Název periodika

Biochemical Journal

ISSN

0264-6021

e-ISSN

—

Svazek periodika

466

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

601-611

Kód UT WoS článku

000351687000015

EID výsledku v databázi Scopus

2-s2.0-84928639745