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Tissue- and species-specific differences in cytochrome c oxidase assembly induced by SURF1 defects
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SYSNO ASEP 0466612 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Tissue- and species-specific differences in cytochrome c oxidase assembly induced by SURF1 defects Author(s) Kovářová, Nikola (FGU-C) RID
Pecina, Petr (FGU-C) RID, ORCID
Nůsková, Hana (FGU-C) RID, ORCID
Vrbacký, Marek (FGU-C) RID, ORCID
Zeviani, M. (IT)
Mráček, Tomáš (FGU-C) RID, ORCID
Viscomi, C. (GB)
Houštěk, Josef (FGU-C) RID, ORCIDSource Title Biochimica Et Biophysica Acta-Molecular Basis of Disease. - : Elsevier - ISSN 0925-4439
Roč. 1862, č. 4 (2016), s. 705-715Number of pages 11 s. Language eng - English Country NL - Netherlands Keywords cytochrome c oxidase ; respiratory supercomplexes ; leigh syndrome ; SURF1−/− mouse knockout ; doxycycline ; pulse-chase Subject RIV EB - Genetics ; Molecular Biology R&D Projects GB14-36804G GA ČR - Czech Science Foundation (CSF) LL1204 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) NT12370 GA MZd - Ministry of Health (MZ) Institutional support FGU-C - RVO:67985823 UT WOS 000372686100021 EID SCOPUS 84958212760 DOI https://doi.org/10.1016/j.bbadis.2016.01.007 Annotation 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. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2017
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