C6ORF66 is an assembly factor of mitochondrial complex

被引：133

作者：

Saada, Ann ^{[1
]}

Edvardson, Simon ^{[2
]}

Rapoport, Matan ^{[4
]}

Shaag, Avraham ^{[1
]}

Amry, Khaled ^{[3
]}

Miller, Chaya ^{[1
]}

Lorberboum-Galski, Haya ^{[4
]}

Elpeleg, Orly ^{[1
]}

机构：

[1] Hadassah Hebrew Univ Med Ctr, Metab Dis Unit, IL-91120 Jerusalem, Israel

[2] Hadassah Hebrew Univ Med Ctr, Pediat Neurol Unit, IL-91120 Jerusalem, Israel

[3] Palestinian Med Relief Soc, Ramallah, Palestine

[4] Hebrew Univ Jerusalem, Sch Med, Dept Cellular Biochem & Human Genet, IL-91010 Jerusalem, Israel

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2008年 / 82卷 / 01期

关键词：

D O I：

10.1016/j.ajhg.2007.08.003

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Homozygosity mapping was performed in five patients from a consanguineous family who presented with infantile mitochondrial encephalomyopathy attributed to isolated NADH:ubiquinone oxidoreductase (complex I) deficiency. This resulted in the identification of a missense mutation in a conserved residue of the C6ORF66 gene, which encodes a 20.2 kDa mitochondrial protein. The mutation was also detected in a patient who presented with antenatal cardiomyopathy. In muscle of two patients, the levels of the C6ORF66 protein and of the fully assembled complex I were markedly reduced. Transfection of the patients' fibroblasts with wild-type C6ORF66 cDNA restored complex I activity. These data suggest that C6ORF66 is an assembly factor of complex I. Interestingly, the C6ORF66 gene product was previously shown to promote breast cancer cell invasiveness.

引用

页码：32 / 38

页数：7

共 24 条

[1] Human CIA30 is involved in the early assembly of mitochondrial complex I and mutations in its gene cause disease [J].

Dunning, C. J. R. ;

McKenzie, M. ;

Sugiana, C. ;

Lazarou, M. ;

Silke, J. ;

Connelly, A. ;

Fletcher, J. M. ;

Kirby, D. M. ;

Thorburn, D. R. ;

Ryan, M. T. .

EMBO JOURNAL, 2007, 26 (13) :3227-3237

[2]

EDVARDSON S, 2007, IN PRESS AM J HUM

[3]

FEARNLEY IM, 2006, METHOD MOL BIOL, V357, P103

[4] Mitochondrial complex I: Structure, function and pathology [J].

Janssen, Rolf J. R. J. ;

Nijtmans, Leo G. ;

van den Heuvel, Lambert P. ;

Smeitink, Jan A. M. .

JOURNAL OF INHERITED METABOLIC DISEASE, 2006, 29 (04) :499-515

[5] HRPAP20: a novel calmodulin-binding protein that increases breast cancer cell invasion [J].

Karp, C. M. ;

Shukla, M. N. ;

Buckley, D. J. ;

Buckley, A. R. .

ONCOGENE, 2007, 26 (12) :1780-1788

[6] Identification of HRPAP20: A novel phosphoprotein that enhances growth and survival in hormone-responsive tumor cells [J].

Karp, CM ;

Pan, HQ ;

Zhang, MY ;

Buckley, DJ ;

Schuler, LA ;

Buckley, AR .

CANCER RESEARCH, 2004, 64 (03) :1016-1025

[7] Cancer's molecular sweet tooth and the Warburg effect [J].

Kim, Jung-whan ;

Dang, Chi V. .

CANCER RESEARCH, 2006, 66 (18) :8927-8930

[8] Respiratory chain complex I deficiency - An underdiagnosed energy generation disorder [J].

Kirby, DM ;

Crawford, M ;

Cleary, MA ;

Dahl, HHM ;

Dennett, X ;

Thorburn, DR .

NEUROLOGY, 1999, 52 (06) :1255-1264

[9] Analysis of the assembly profiles for mitochondrial- and nuclear-DNA-encoded subunits into complex I [J].

Lazarou, Michael ;

McKenzie, Matthew ;

Ohtake, Akira ;

Thorburn, David R. ;

Ryan, Michael T. .

MOLECULAR AND CELLULAR BIOLOGY, 2007, 27 (12) :4228-4237

[10] Recurrent de novo mitochondrial DNA mutations in respiratory chain deficiency [J].

Lebon, S ;

Chol, M ;

Benit, P ;

Mugnier, C ;

Chretien, D ;

Giurgea, I ;

Kern, I ;

Girardin, E ;

Hertz-Pannier, L ;

de Lonlay, P ;

Rötig, A ;

Rustin, P ;

Munnich, A .

JOURNAL OF MEDICAL GENETICS, 2003, 40 (12) :896-899

← 1 2 3 →