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ACAD9, a complex I assembly factor with a moonlighting function in fatty acid oxidation deficiencies. / Nouws, Jessica; te Brinke, Heleen; Nijtmans, Leo G. et al.

In: Human molecular genetics, Vol. 23, No. 5, 2014, p. 1311-1319.

Research output: Contribution to journalArticleAcademicpeer-review

Harvard

Nouws, J, te Brinke, H, Nijtmans, LG & Houten, SM 2014, 'ACAD9, a complex I assembly factor with a moonlighting function in fatty acid oxidation deficiencies', Human molecular genetics, vol. 23, no. 5, pp. 1311-1319. https://doi.org/10.1093/hmg/ddt521

APA

Vancouver

Nouws J, te Brinke H, Nijtmans LG, Houten SM. ACAD9, a complex I assembly factor with a moonlighting function in fatty acid oxidation deficiencies. Human molecular genetics. 2014;23(5):1311-1319. doi: 10.1093/hmg/ddt521

Author

Nouws, Jessica ; te Brinke, Heleen ; Nijtmans, Leo G. et al. / ACAD9, a complex I assembly factor with a moonlighting function in fatty acid oxidation deficiencies. In: Human molecular genetics. 2014 ; Vol. 23, No. 5. pp. 1311-1319.

BibTeX

@article{df1775c515924e95bebfb1b61b24ee8d,
title = "ACAD9, a complex I assembly factor with a moonlighting function in fatty acid oxidation deficiencies",
abstract = "Oxidative phosphorylation and fatty acid oxidation are two major metabolic pathways in mitochondria. Acyl-CoA dehydrogenase 9 (ACAD9), an enzyme assumed to play a role in fatty acid oxidation, was recently identified as a factor involved in complex I biogenesis. Here we further investigated the role of ACAD9's enzymatic activity in fatty acid oxidation and complex I biogenesis. We provide evidence indicating that ACAD9 displays enzyme activity in vivo. Knockdown experiments in very-long-chain acyl-CoA dehydrogenase (VLCAD)-deficient fibroblasts revealed that ACAD9 is responsible for the production of C14:1-carnitine from oleate and C12-carnitine from palmitate. These results explain the origin of these obscure acylcarnitines that are used to diagnose VLCAD deficiency in humans. Knockdown of ACAD9 in control fibroblasts did not reveal changes in the acylcarnitine profiles upon fatty acid loading. Next, we investigated whether catalytic activity of ACAD9 was necessary for complex I biogenesis. Catalytically inactive ACAD9 gave partial-to-complete rescue of complex I biogenesis in ACAD9-deficient cells and was incorporated in high-molecular-weight assembly intermediates. Our results underscore the importance of the ACAD9 protein in complex I assembly and suggest that the enzymatic activity is a rudiment of the duplication event",
author = "Jessica Nouws and {te Brinke}, Heleen and Nijtmans, {Leo G.} and Houten, {Sander M.}",
year = "2014",
doi = "10.1093/hmg/ddt521",
language = "English",
volume = "23",
pages = "1311--1319",
journal = "Human molecular genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "5",

}

RIS

TY - JOUR

T1 - ACAD9, a complex I assembly factor with a moonlighting function in fatty acid oxidation deficiencies

AU - Nouws, Jessica

AU - te Brinke, Heleen

AU - Nijtmans, Leo G.

AU - Houten, Sander M.

PY - 2014

Y1 - 2014

N2 - Oxidative phosphorylation and fatty acid oxidation are two major metabolic pathways in mitochondria. Acyl-CoA dehydrogenase 9 (ACAD9), an enzyme assumed to play a role in fatty acid oxidation, was recently identified as a factor involved in complex I biogenesis. Here we further investigated the role of ACAD9's enzymatic activity in fatty acid oxidation and complex I biogenesis. We provide evidence indicating that ACAD9 displays enzyme activity in vivo. Knockdown experiments in very-long-chain acyl-CoA dehydrogenase (VLCAD)-deficient fibroblasts revealed that ACAD9 is responsible for the production of C14:1-carnitine from oleate and C12-carnitine from palmitate. These results explain the origin of these obscure acylcarnitines that are used to diagnose VLCAD deficiency in humans. Knockdown of ACAD9 in control fibroblasts did not reveal changes in the acylcarnitine profiles upon fatty acid loading. Next, we investigated whether catalytic activity of ACAD9 was necessary for complex I biogenesis. Catalytically inactive ACAD9 gave partial-to-complete rescue of complex I biogenesis in ACAD9-deficient cells and was incorporated in high-molecular-weight assembly intermediates. Our results underscore the importance of the ACAD9 protein in complex I assembly and suggest that the enzymatic activity is a rudiment of the duplication event

AB - Oxidative phosphorylation and fatty acid oxidation are two major metabolic pathways in mitochondria. Acyl-CoA dehydrogenase 9 (ACAD9), an enzyme assumed to play a role in fatty acid oxidation, was recently identified as a factor involved in complex I biogenesis. Here we further investigated the role of ACAD9's enzymatic activity in fatty acid oxidation and complex I biogenesis. We provide evidence indicating that ACAD9 displays enzyme activity in vivo. Knockdown experiments in very-long-chain acyl-CoA dehydrogenase (VLCAD)-deficient fibroblasts revealed that ACAD9 is responsible for the production of C14:1-carnitine from oleate and C12-carnitine from palmitate. These results explain the origin of these obscure acylcarnitines that are used to diagnose VLCAD deficiency in humans. Knockdown of ACAD9 in control fibroblasts did not reveal changes in the acylcarnitine profiles upon fatty acid loading. Next, we investigated whether catalytic activity of ACAD9 was necessary for complex I biogenesis. Catalytically inactive ACAD9 gave partial-to-complete rescue of complex I biogenesis in ACAD9-deficient cells and was incorporated in high-molecular-weight assembly intermediates. Our results underscore the importance of the ACAD9 protein in complex I assembly and suggest that the enzymatic activity is a rudiment of the duplication event

U2 - 10.1093/hmg/ddt521

DO - 10.1093/hmg/ddt521

M3 - Article

C2 - 24158852

VL - 23

SP - 1311

EP - 1319

JO - Human molecular genetics

JF - Human molecular genetics

SN - 0964-6906

IS - 5

ER -

ID: 2231994