Tissue- and species-specific differences in cytochrome c oxidase assembly induced by SURF1 defects

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F16%3A00466612" target="_blank" >RIV/67985823:_____/16:00466612 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.bbadis.2016.01.007" target="_blank" >http://dx.doi.org/10.1016/j.bbadis.2016.01.007</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bbadis.2016.01.007" target="_blank" >10.1016/j.bbadis.2016.01.007</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Tissue- and species-specific differences in cytochrome c oxidase assembly induced by SURF1 defects

Popis výsledku v původním jazyce

Mitochondrial protein SURF1 is a specific assembly factor of cytochrome c oxidase (COX), but its function is poorly understood. SURF1 gene mutations cause a severe COX deficiency manifesting as the Leigh syndrome in humans, whereas in mice SURF1/ knockout leads only to a mild COX defect. We used SURF1/ mouse model for detailed analysis of disturbed COX assembly and COX ability to incorporate into respiratory supercomplexes (SCs) in different tissues and fibroblasts. Furthermore, we compared fibroblasts from SURF1/ mouse and SURF1 patients to reveal interspecies differences in kinetics of COX biogenesis using 2D electrophoresis, immunodetection, arrest of mitochondrial proteosynthesis and pulse-chase metabolic labeling. The crucial differences observed are an accumulation of abundant COX1 assembly intermediates, low content of COX monomer and preferential recruitment of COX into I–III–IV SCs in SURF1 patient fibroblasts, whereas SURF1/ mouse fibroblasts were characterized by low content of COX1 assembly intermediates and milder decrease in COX monomer, which appeared more stable. This pattern was even less pronounced in SURF1/ mouse liver and brain. Both the control and SURF1/ mice revealed only negligible formation of the I–III–IV SCs and marked tissue differences in the contents of COX dimer and III2–IV SCs, also less noticeable in liver and brain than in heart and muscle. Our studies support the view that COX assembly is much more dependent on SURF1 in humans than in mice. We also demonstrate markedly lower ability of mouse COX to form I–III–IV supercomplexes, pointing to tissue-specific and species-specific differences in COX biogenesis.

Název v anglickém jazyce

Tissue- and species-specific differences in cytochrome c oxidase assembly induced by SURF1 defects

Popis výsledku anglicky

Mitochondrial protein SURF1 is a specific assembly factor of cytochrome c oxidase (COX), but its function is poorly understood. SURF1 gene mutations cause a severe COX deficiency manifesting as the Leigh syndrome in humans, whereas in mice SURF1/ knockout leads only to a mild COX defect. We used SURF1/ mouse model for detailed analysis of disturbed COX assembly and COX ability to incorporate into respiratory supercomplexes (SCs) in different tissues and fibroblasts. Furthermore, we compared fibroblasts from SURF1/ mouse and SURF1 patients to reveal interspecies differences in kinetics of COX biogenesis using 2D electrophoresis, immunodetection, arrest of mitochondrial proteosynthesis and pulse-chase metabolic labeling. The crucial differences observed are an accumulation of abundant COX1 assembly intermediates, low content of COX monomer and preferential recruitment of COX into I–III–IV SCs in SURF1 patient fibroblasts, whereas SURF1/ mouse fibroblasts were characterized by low content of COX1 assembly intermediates and milder decrease in COX monomer, which appeared more stable. This pattern was even less pronounced in SURF1/ mouse liver and brain. Both the control and SURF1/ mice revealed only negligible formation of the I–III–IV SCs and marked tissue differences in the contents of COX dimer and III2–IV SCs, also less noticeable in liver and brain than in heart and muscle. Our studies support the view that COX assembly is much more dependent on SURF1 in humans than in mice. We also demonstrate markedly lower ability of mouse COX to form I–III–IV supercomplexes, pointing to tissue-specific and species-specific differences in COX biogenesis.

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

2016

Kód důvěrnosti údajů

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

Název periodika

Biochimica Et Biophysica Acta-Molecular Basis of Disease

ISSN

0925-4439

e-ISSN

—

Svazek periodika

1862

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

11

Strana od-do

705-715

Kód UT WoS článku

000372686100021

EID výsledku v databázi Scopus

2-s2.0-84958212760