TMEM70 facilitates biogenesis of mammalian ATP synthase by promoting subunit c incorporation into the rotor structure of the enzyme

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F19%3A00520774" target="_blank" >RIV/67985823:_____/19:00520774 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68378050:_____/19:00520774 RIV/61388963:_____/19:00520846

Výsledek na webu

<a href="https://doi.org/10.1096/fj.201900685RR" target="_blank" >https://doi.org/10.1096/fj.201900685RR</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1096/fj.201900685RR" target="_blank" >10.1096/fj.201900685RR</a>

Jazyk výsledku

angličtina

Název v původním jazyce

TMEM70 facilitates biogenesis of mammalian ATP synthase by promoting subunit c incorporation into the rotor structure of the enzyme

Popis výsledku v původním jazyce

Biogenesis of F1Fo ATP synthase depends on TMEM70 protein, localized in the inner mitochondrial membrane of higher eukaryotes. TMEM70 absence causes severe ATP synthase deficiency and leads to a neonatal mitochondrial encephalo-cardiomyopathy in humans. However, the exact biochemical function of TMEM70 remains unknown. Using TMEM70 conditional knockout in mice we show that absence of TMEM70 impairs the early stage of enzyme biogenesis by preventing incorporation of hydrophobic subunit c into rotor structure of the enzyme. This results in formation of an incomplete, pathological enzyme complex lacking Fo proton channel composed of subunits c and a. We demonstrated direct interaction between TMEM70 and subunit c and showed that overexpression of subunit c in TMEM70‐/‐ cells partially rescued TMEM70 defect. Accordingly, TMEM70 knockdown prevented subunit c accumulation otherwise observed in F1‐deficient cells. Altogether, we identified TMEM70 as specific ancillary factor for subunit c.

Název v anglickém jazyce

TMEM70 facilitates biogenesis of mammalian ATP synthase by promoting subunit c incorporation into the rotor structure of the enzyme

Popis výsledku anglicky

Biogenesis of F1Fo ATP synthase depends on TMEM70 protein, localized in the inner mitochondrial membrane of higher eukaryotes. TMEM70 absence causes severe ATP synthase deficiency and leads to a neonatal mitochondrial encephalo-cardiomyopathy in humans. However, the exact biochemical function of TMEM70 remains unknown. Using TMEM70 conditional knockout in mice we show that absence of TMEM70 impairs the early stage of enzyme biogenesis by preventing incorporation of hydrophobic subunit c into rotor structure of the enzyme. This results in formation of an incomplete, pathological enzyme complex lacking Fo proton channel composed of subunits c and a. We demonstrated direct interaction between TMEM70 and subunit c and showed that overexpression of subunit c in TMEM70‐/‐ cells partially rescued TMEM70 defect. Accordingly, TMEM70 knockdown prevented subunit c accumulation otherwise observed in F1‐deficient cells. Altogether, we identified TMEM70 as specific ancillary factor for subunit c.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10603 - Genetics and heredity (medical genetics to be 3)

Projekt

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

Návaznosti

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

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

FASEB Journal

ISSN

0892-6638

e-ISSN

—

Svazek periodika

33

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

15

Strana od-do

14103-14117

Kód UT WoS článku

000507466100080

EID výsledku v databázi Scopus

2-s2.0-85076063076