A lethal defect of mitochondrial and peroxisomal fission

被引：568

作者：

Waterham, Hans R.

Koster, Janet

van Roermund, Carlo W. T.

Mooyer, Petra A. W.

Wanders, Ronald J. A.

Leonard, Andiarnes V.

机构：

[1] Univ Amsterdam, Acad Med Ctr, Dept Clin Chem, Lab Genet Metab Dis, NL-1105 AZ Amsterdam, Netherlands

[2] Univ Amsterdam, Acad Med Ctr, Dept Pediat, Lab Genet Metab Dis, NL-1105 AZ Amsterdam, Netherlands

[3] UCL, Inst Child Hlth, Dept Pediat, London WC1E 6BT, England

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2007年 / 356卷 / 17期

关键词：

D O I：

10.1056/NEJMoa064436

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

We report on a newborn girl with microcephaly, abnormal brain development, optic atrophy and hypoplasia, persistent lactic acidemia, and a mildly elevated plasma concentration of very-long-chain fatty acids. We found a defect of the fission of both mitochondria and peroxisomes, as well as a heterozygous, dominant-negative mutation in the dynamin-like protein 1 gene (DLP1). The DLP1 protein has previously been implicated, in vitro, in the fission of both these organelles. Overexpression of the mutant DLP1 in control cells reproduced the fission defect. Our findings are representative of a class of disease characterized by defects in both mitochondria and peroxisomes.

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页码：1736 / 1741

页数：6

相关论文

共 25 条

[1] OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28 [J].

Alexander, C ;

Votruba, M ;

Pesch, UEA ;

Thiselton, DL ;

Mayer, S ;

Moore, A ;

Rodriguez, M ;

Kellner, U ;

Leo-Kottler, B ;

Auburger, G ;

Bhattacharya, SS ;

Wissinger, B .

NATURE GENETICS, 2000, 26 (02) :211-215

[2] Emerging functions of mammalian mitochondrial fusion and fission [J].

Chen, HC ;

Chan, DC .

HUMAN MOLECULAR GENETICS, 2005, 14 :R283-R289

[3] The expanding phenotype of mitochondrial myopathy [J].

DiMauro, S ;

Gurgel-Giannetti, J .

CURRENT OPINION IN NEUROLOGY, 2005, 18 (05) :538-542

[4] Diagnostic value of succinate ubiquinone reductase activity in the identification of patients with mitochondrial DNA depletion [J].

Hargreaves, IP ;

Rahman, S ;

Guthrie, P ;

Taanman, JW ;

Leonard, JV ;

Land, JM ;

Heales, SJR .

JOURNAL OF INHERITED METABOLIC DISEASE, 2002, 25 (01) :7-16

[5] Genomic organization, alternative splicing, and promoter analysis of human dynamin-like protein gene [J].

Howng, SL ;

Sy, WD ;

Cheng, TS ;

Lieu, AS ;

Wang, CH ;

Tzou, WS ;

Cho, CL ;

Hong, YR .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2004, 314 (03) :766-772

[6]

James DI, 2004, J BIOL CHEM, V279, P36166

[7] hFis1, a novel component of the mammalian mitochondrial fission machinery [J].

James, DI ;

Parone, PA ;

Mattenberger, Y ;

Martinou, JC .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (38) :36373-36379

[8] A role for Fis1 in both mitochondrial and peroxisomal fission in mammalian cells [J].

Koch, A ;

Yoon, Y ;

Bonekamp, NA ;

McNiven, MA ;

Schrader, M .

MOLECULAR BIOLOGY OF THE CELL, 2005, 16 (11) :5077-5086

[9] Dynamin-like protein 1 is involved in peroxisomal fission [J].

Koch, A ;

Thiemann, M ;

Grabenbauer, M ;

Yoon, Y ;

McNiven, MA ;

Schrader, M .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (10) :8597-8605

[10] The dynamin-like GTPase DLP1 is essential for peroxisome division and is recruited to peroxisomes in part by PEX11 [J].

Li, XL ;

Gould, SJ .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (19) :17012-17020