Acyl-CoA Dehydrogenase 9 Is Required for the Biogenesis of Oxidative Phosphorylation Complex I

被引：152

作者：

Nouws, Jessica ^{[1
]}

Nijtmans, Leo ^{[1
]}

Houten, Sander M. ^{[5
,6
]}

van den Brand, Mariel ^{[1
]}

Huynen, Martijn ^{[2
]}

Venselaar, Hanka ^{[2
]}

Hoefs, Saskia ^{[1
]}

Gloerich, Jolein ^{[3
]}

Kronick, Jonathan ^{[7
]}

Hutchin, Timothy ^{[8
]}

Willems, Peter ^{[4
]}

Rodenburg, Richard ^{[1
]}

Wanders, Ronald ^{[5
,6
]}

van den Heuvel, Lambert ^{[1
]}

Smeitink, Jan ^{[1
]}

Vogel, Rutger O. ^{[1
]}

机构：

[1] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mitochondrial Disorders, Dept Pediat, NL-6500 HB Nijmegen, Netherlands

[2] Radboud Univ Nijmegen, Med Ctr, Ctr Mol & Biomol Informat, NL-6500 HB Nijmegen, Netherlands

[3] Radboud Univ Nijmegen, Med Ctr, Nijmegen Prote Facil, NL-6500 HB Nijmegen, Netherlands

[4] Radboud Univ Nijmegen, Med Ctr, Dept Biochem, Nijmegen Ctr Mol Life Sci, NL-6500 HB Nijmegen, Netherlands

[5] Univ Amsterdam, Dept Pediat, Lab Genet Metab Dis, Emma Childrens Hosp,Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands

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

[7] Dalhousie Univ, Dept Pediat, IWK Hlth Ctr, Halifax, NS B3K 6R8, Canada

[8] Birmingham Childrens Hosp, Birmingham B4 6DH, W Midlands, England

来源：

CELL METABOLISM | 2010年 / 12卷 / 03期

关键词：

MITOCHONDRIAL INTERMEDIATE PEPTIDASE; RESPIRATORY-CHAIN; BETA-OXIDATION; CYTOCHROME-C; MUTATION; GENE; DEFICIENCY; SPECIFICITY; CHAPERONE; COENZYME;

D O I：

10.1016/j.cmet.2010.08.002

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Acyl-CoA dehydrogenase 9 (ACAD9) is a recently identified member of the acyl-CoA dehydrogenase family. It closely resembles very long-chain acyl-CoA dehydrogenase (VLCAD), involved in mitochondria! (3 oxidation of long-chain fatty acids. Contrary to its previously proposed involvement in fatty acid oxidation, we describe a role for ACAD9 in oxidative phosphorylation. ACAD9 binds complex I assembly factors NDUFAF1 and Ecsit and is specifically required for the assembly of complex I. Furthermore, ACAD9 mutations result in complex I deficiency and not in disturbed long-chain fatty acid oxidation. This strongly contrasts with its evolutionary ancestor VLCAD, which we show is not required for complex I assembly and clearly plays a role in fatty acid oxidation. Our results demonstrate that two closely related metabolic enzymes have diverged at the root of the vertebrate lineage to function in two separate mitochondrial metabolic pathways and have clinical implications for the diagnosis of complex I deficiency.

引用

页码：283 / 294

页数：12

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