Počet záznamů: 1
Loss of COX4I1 Leads to Combined Respiratory Chain Deficiency and Impaired Mitochondrial Protein Synthesis
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SYSNO ASEP 0541622 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Loss of COX4I1 Leads to Combined Respiratory Chain Deficiency and Impaired Mitochondrial Protein Synthesis Tvůrce(i) Čunátová, Kristýna (FGU-C) RID, ORCID
Pajuelo-Reguera, David (FGU-C) RID, ORCID, SAI
Vrbacký, Marek (FGU-C) RID, ORCID
Fernández-Vizarra, E. (GB)
Ding, SJ. (GB)
Fearnley, I.M. (GB)
Zeviani, M. (GB)
Houštěk, Josef (FGU-C) RID, ORCID
Mráček, Tomáš (FGU-C) RID, ORCID
Pecina, Petr (FGU-C) RID, ORCIDČíslo článku 369 Zdroj.dok. Cells. - : MDPI
Roč. 10, č. 2 (2021)Poč.str. 18 s. Jazyk dok. eng - angličtina Země vyd. CH - Švýcarsko Klíč. slova mitochondria ; OXPHOS ; cI ; COX ; cIV ; COX4 ; knock-out ; cIV assembly ; complex I ; biogenesis interdependency ; complexome profiling ; mitochondrial protein synthesis Vědní obor RIV CE - Biochemie Obor OECD Biochemistry and molecular biology CEP GA16-13671S GA ČR - Grantová agentura ČR NV19-07-00149 GA MZd - Ministerstvo zdravotnictví ED1.1.00/02.0109 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora FGU-C - RVO:67985823 UT WOS 000622356000001 EID SCOPUS 85101349220 DOI 10.3390/cells10020369 Anotace The oxidative phosphorylation (OXPHOS) system localized in the inner mitochondrial membrane secures production of the majority of ATP in mammalian organisms. Individual OXPHOS complexes form supramolecular assemblies termed supercomplexes. The complexes are linked not only by their function but also by interdependency of individual complex biogenesis or maintenance. For instance, cytochrome c oxidase (cIV) or cytochrome bc1 complex (cIII) deficiencies affect the level of fully assembled NADH dehydrogenase (cI) in monomeric as well as supercomplex forms. It was hypothesized that cI is affected at the level of enzyme assembly as well as at the level of cI stability and maintenance. However, the true nature of interdependency between cI and cIV is not fully understood yet. We used a HEK293 cellular model where the COX4 subunit was completely knocked out, serving as an ideal system to study interdependency of cI and cIV, as early phases of cIV assembly process were disrupted. Total absence of cIV was accompanied by profound deficiency of cI, documented by decrease in the levels of cI subunits and significantly reduced amount of assembled cI. Supercomplexes assembled from cI, cIII, and cIV were missing in COX4I1 knock-out (KO) due to loss of cIV and decrease in cI amount. Pulse-chase metabolic labeling of mitochondrial DNA (mtDNA)-encoded proteins uncovered a decrease in the translation of cIV and cI subunits. Moreover, partial impairment of mitochondrial protein synthesis correlated with decreased content of mitochondrial ribosomal proteins. In addition, complexome profiling revealed accumulation of cI assembly intermediates, indicating that cI biogenesis, rather than stability, was affected. We propose that attenuation of mitochondrial protein synthesis caused by cIV deficiency represents one of the mechanisms, which may impair biogenesis of cI. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2022 Elektronická adresa https://www.mdpi.com/2073-4409/10/2/369
Počet záznamů: 1