Tissue-specific cytochrome c oxidase assembly defects due to mutations in SCO2 and SURF1

被引:85
|
作者
Stiburek, L
Vesela, K
Hansikova, H
Pecina, P
Tesarova, M
Cerna, L
Houstek, J
Zeman, J
机构
[1] Charles Univ, Fac Med 1, Dept Pediat, Prague 12808, Czech Republic
[2] Charles Univ, Fac Med 1, Ctr Appl Genom, Prague 12808, Czech Republic
[3] Acad Sci Czech Republ, Inst Physiol, Dept Bioenerget, CR-14220 Prague, Czech Republic
关键词
assembly pathway; Cu-A centre; cytochrome c oxidase; mitochondria; SCO2; SURF1;
D O I
10.1042/BJ20050807
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The biogenesis of eukaryotic COX (cytochrome c oxidase) requires several accessory proteins in addition to structural subunits and prosthetic groups. We have analysed the assembly state of COX and SC02 protein levels in various tissues of six patients with mutations in SC02 and SURF1. SC02 is a copper-binding protein presumably involved in formation of the Cu-A centre of the COX2 subunit. The function of SURF1 is unknown. Immunoblot analysis of native gels demonstrated that COX holoenzyme is reduced to 10-20% in skeletal muscle and brain of SC02 and SURF1 patients and to 10-30% in heart of SC02 patients, whereas liver of SC02 patients' contained normal holoenzyme levels. The steady-state levels of mutant SC02 protein ranged from 0 to 20% in different SC02 patient tissues. In addition, eight distinct COX subcomplexes and unassembled subunits were found, some of them identical with known assembly intermediates of the human enzyme. Heart, brain and skeletal muscle of SC02 patients contained accumulated levels of the COX1(.)COX4(.) COX5A subcomplex, three COX1-containing subcomplexes, a COX4(.)COX5A subcomplex and two subcomplexes composed of only COX4 or COX5A. The accumulation of COX 1(.)COX4(.) COX5A subcomplex, along with the virtual absence of free COX2, suggests that the lack of the Cu-A centre may result in decreased stability of COX2. The appearance of COX4(.)COX5A subcomplex indicates that association of these nucleus-encoded subunits probably precedes their addition to COX1 during the assembly process. Finally, the consequences of SC02 and SURF1 mutations suggest the existence of tissue-specific functional differences of these proteins that may serve different tissue-specific requirements for the regulation of COX biogenesis.
引用
收藏
页码:625 / 632
页数:8
相关论文
共 50 条
  • [1] Tissue-specific cytochrome c oxidase assembly defects due to mutation in SCO2
    Stiburek, L
    Vesela, K
    Hansikova, H
    Tesarova, M
    Houstek, J
    Zeman, J
    BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 2004, 1657 : 71 - 71
  • [2] Tissue- and species-specific differences in cytochrome c oxidase assembly induced by SURF1 defects
    Kovarova, Nikola
    Pecina, Petr
    Nuskova, Hana
    Vrbacky, Marek
    Zeviani, Massimo
    Mracek, Tomas
    Viscomi, Carlo
    Houstek, Josef
    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2016, 1862 (04): : 705 - 715
  • [3] TISSUE COPPER LEVELS IN CHILDREN CARRYING MUTATIONS IN SCO1, SCO2 AND SURF1
    Hansikova, H.
    Vesela, K.
    Tesarova, M.
    Vondrackova, A.
    Fornuskova, D.
    Honzik, T.
    Stiburek, L.
    Zeman, J.
    JOURNAL OF INHERITED METABOLIC DISEASE, 2011, 34 : S166 - S166
  • [4] Cytochrome c oxidase deficiency due to mutations in SCO2 gene
    Vesela, K
    Hansikova, H
    Tesarova, M
    Martasek, P
    Houstek, J
    Zeman, J
    AMERICAN JOURNAL OF HUMAN GENETICS, 2003, 73 (05) : 574 - 574
  • [5] Association of mutations in SCO2, a cytochrome c oxidase assembly gene, with early fetal lethality
    Tay, SKH
    Shanske, S
    Kaplan, P
    DiMauro, S
    ARCHIVES OF NEUROLOGY, 2004, 61 (06) : 950 - 952
  • [6] Missense mutations in SURF1 associated with deficient cytochrome c oxidase assembly in Leigh syndrome patients
    A. Poyau
    K. Buchet
    M. Fouad Bouzidi
    M.-T. Zabot
    B. Echenne
    J. Yao
    E.A. Shoubridge
    C. Godinot
    Human Genetics, 2000, 106 (2) : 194 - 205
  • [7] Missense mutations in SURF1 associated with deficient cytochrome c oxidase assembly in Leigh syndrome patients
    Poyau, A
    Buchet, K
    Bouzidi, MF
    Zabot, MT
    Echenne, B
    Yao, JB
    Shoubridge, EA
    Godinot, C
    HUMAN GENETICS, 2000, 106 (02) : 194 - 205
  • [8] Functional alteration of cytochrome c oxidase by SURF1 mutations in Leigh syndrome
    Pecina, P
    Capková, M
    Chowdhury, SKR
    Drahota, Z
    Dubot, A
    Vojtísková, A
    Hansíková, H
    Houst'ková, H
    Zeman, J
    Godinot, C
    Houstek, J
    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2003, 1639 (01): : 53 - 63
  • [9] Structural analysis of tissues affected by cytochrome C oxidase deficiency due to mutations in the SCO2 gene
    Vesela, Katerina
    Hulkova, Helena
    Hansikova, Hana
    Zeman, Jiri
    Elleder, Milan
    APMIS, 2008, 116 (01) : 41 - 49
  • [10] Two novel mutations of SURF1 in Leigh syndrome with cytochrome c oxidase deficiency
    Teraoka M.
    Yokoyama Y.
    Ninomiya S.
    Inoue C.
    Yamashita S.
    Seino Y.
    Human Genetics, 1999, 105 (6) : 560 - 563