-
Something wrong with this record ?
A pseudoautosomal glycosylation disorder prompts the revision of dolichol biosynthesis
MP. Wilson, T. Kentache, CR. Althoff, C. Schulz, G. de Bettignies, G. Mateu Cabrera, L. Cimbalistiene, B. Burnyte, G. Yoon, G. Costain, S. Vuillaumier-Barrot, D. Cheillan, D. Rymen, L. Rychtarova, H. Hansikova, M. Bury, JP. Dewulf, F. Caligiore,...
Language English Country United States
Document type Journal Article
NLK
Cell Press Free Archives
from 1995-01-01 to 1 year ago
Free Medical Journals
from 1995 to 1 year ago
Open Access Digital Library
from 1995-01-01
- MeSH
- 3-Oxo-5-alpha-Steroid 4-Dehydrogenase metabolism genetics MeSH
- Dolichols * metabolism biosynthesis MeSH
- Glycosylation MeSH
- Humans MeSH
- Membrane Proteins metabolism genetics MeSH
- Mutation, Missense MeSH
- Congenital Disorders of Glycosylation metabolism genetics MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Dolichol is a lipid critical for N-glycosylation as a carrier for activated sugars and nascent oligosaccharides. It is commonly thought to be directly produced from polyprenol by the enzyme SRD5A3. Instead, we found that dolichol synthesis requires a three-step detour involving additional metabolites, where SRD5A3 catalyzes only the second reaction. The first and third steps are performed by DHRSX, whose gene resides on the pseudoautosomal regions of the X and Y chromosomes. Accordingly, we report a pseudoautosomal-recessive disease presenting as a congenital disorder of glycosylation in patients with missense variants in DHRSX (DHRSX-CDG). Of note, DHRSX has a unique dual substrate and cofactor specificity, allowing it to act as a NAD+-dependent dehydrogenase and as a NADPH-dependent reductase in two non-consecutive steps. Thus, our work reveals unexpected complexity in the terminal steps of dolichol biosynthesis. Furthermore, we provide insights into the mechanism by which dolichol metabolism defects contribute to disease.
Department of Molecular Genetics University of Toronto Toronto ON Canada
Department of Paediatrics University of Toronto Toronto ON Canada
Department of Pediatrics Center for Metabolic Diseases University Hospitals Leuven Leuven Belgium
Division of Clinical and Metabolic Genetics Hospital for Sick Children Toronto ON Canada
Division of Neurology Hospital for Sick Children Toronto ON Canada
Institute of Biomedical Sciences Faculty of Medicine Vilnius University Vilnius Lithuania
Laboratoire Carmen Inserm U1060 INRAE UMR1397 Université Claude Bernard Lyon 1 Lyon France
Laboratory for Molecular Diagnosis Center for Human Genetics KU Leuven Leuven Belgium
Metabolic Research Group de Duve Institute Université Catholique de Louvain Brussels Belgium
Program in Genetics and Genome Biology SickKids Research Institute Toronto ON Canada
Service Biochimie et Biologie Moléculaire Hospices Civils de Lyon
Univ Lille CNRS UMR 8576 UGSF Unité de Glycobiologie Structurale et Fonctionnelle 59000 Lille France
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc24019762
- 003
- CZ-PrNML
- 005
- 20241024111009.0
- 007
- ta
- 008
- 241015s2024 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.cell.2024.04.041 $2 doi
- 035 __
- $a (PubMed)38821050
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Wilson, Matthew P $u Laboratory for Molecular Diagnosis, Center for Human Genetics, KU Leuven, Leuven, Belgium
- 245 12
- $a A pseudoautosomal glycosylation disorder prompts the revision of dolichol biosynthesis / $c MP. Wilson, T. Kentache, CR. Althoff, C. Schulz, G. de Bettignies, G. Mateu Cabrera, L. Cimbalistiene, B. Burnyte, G. Yoon, G. Costain, S. Vuillaumier-Barrot, D. Cheillan, D. Rymen, L. Rychtarova, H. Hansikova, M. Bury, JP. Dewulf, F. Caligiore, J. Jaeken, V. Cantagrel, E. Van Schaftingen, G. Matthijs, F. Foulquier, GT. Bommer
- 520 9_
- $a Dolichol is a lipid critical for N-glycosylation as a carrier for activated sugars and nascent oligosaccharides. It is commonly thought to be directly produced from polyprenol by the enzyme SRD5A3. Instead, we found that dolichol synthesis requires a three-step detour involving additional metabolites, where SRD5A3 catalyzes only the second reaction. The first and third steps are performed by DHRSX, whose gene resides on the pseudoautosomal regions of the X and Y chromosomes. Accordingly, we report a pseudoautosomal-recessive disease presenting as a congenital disorder of glycosylation in patients with missense variants in DHRSX (DHRSX-CDG). Of note, DHRSX has a unique dual substrate and cofactor specificity, allowing it to act as a NAD+-dependent dehydrogenase and as a NADPH-dependent reductase in two non-consecutive steps. Thus, our work reveals unexpected complexity in the terminal steps of dolichol biosynthesis. Furthermore, we provide insights into the mechanism by which dolichol metabolism defects contribute to disease.
- 650 12
- $a dolichol $x metabolismus $x biosyntéza $7 D004286
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a glykosylace $7 D006031
- 650 _2
- $a 3-oxo-5-alfa-steroid-4-dehydrogenasa $x metabolismus $x genetika $7 D013741
- 650 _2
- $a membránové proteiny $x metabolismus $x genetika $7 D008565
- 650 _2
- $a vrozené poruchy glykosylace $x metabolismus $x genetika $7 D018981
- 650 _2
- $a mužské pohlaví $7 D008297
- 650 _2
- $a missense mutace $7 D020125
- 650 _2
- $a ženské pohlaví $7 D005260
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Kentache, Takfarinas $u Metabolic Research Group, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; WELBIO Department, WEL Research Institute, Wavre, Belgium
- 700 1_
- $a Althoff, Charlotte R $u Laboratory for Molecular Diagnosis, Center for Human Genetics, KU Leuven, Leuven, Belgium; Univ. Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France
- 700 1_
- $a Schulz, Céline $u Univ. Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France
- 700 1_
- $a de Bettignies, Geoffroy $u Univ. Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France
- 700 1_
- $a Mateu Cabrera, Gisèle $u Laboratory for Molecular Diagnosis, Center for Human Genetics, KU Leuven, Leuven, Belgium
- 700 1_
- $a Cimbalistiene, Loreta $u Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
- 700 1_
- $a Burnyte, Birute $u Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
- 700 1_
- $a Yoon, Grace $u Division of Clinical and Metabolic Genetics, Hospital for Sick Children, Toronto, ON, Canada; Division of Neurology, Hospital for Sick Children, Toronto, ON, Canada; Department of Paediatrics, University of Toronto, Toronto, ON, Canada
- 700 1_
- $a Costain, Gregory $u Division of Clinical and Metabolic Genetics, Hospital for Sick Children, Toronto, ON, Canada; Department of Paediatrics, University of Toronto, Toronto, ON, Canada; Program in Genetics and Genome Biology, SickKids Research Institute, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
- 700 1_
- $a Vuillaumier-Barrot, Sandrine $u AP-HP, Biochimie Métabolique et Cellulaire and Département de Génétique, Hôpital Bichat-Claude Bernard, and Université de Paris, Faculté de Médecine Xavier Bichat, INSERM U1149, CRI, Paris, France
- 700 1_
- $a Cheillan, David $u Service Biochimie et Biologie Moléculaire - Hospices Civils de Lyon; Laboratoire Carmen - Inserm U1060, INRAE UMR1397, Université Claude Bernard Lyon 1, Lyon, France
- 700 1_
- $a Rymen, Daisy $u Department of Pediatrics, Center for Metabolic Diseases, University Hospitals Leuven, Leuven, Belgium
- 700 1_
- $a Rychtarova, Lucie $u Laboratory for Study of Mitochondrial Disorders, Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine and General University Hospital in Prague, Charles University, Prague, Czechia
- 700 1_
- $a Hansikova, Hana $u Laboratory for Study of Mitochondrial Disorders, Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine and General University Hospital in Prague, Charles University, Prague, Czechia
- 700 1_
- $a Bury, Marina $u Metabolic Research Group, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; WELBIO Department, WEL Research Institute, Wavre, Belgium
- 700 1_
- $a Dewulf, Joseph P $u Metabolic Research Group, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; WELBIO Department, WEL Research Institute, Wavre, Belgium
- 700 1_
- $a Caligiore, Francesco $u Metabolic Research Group, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; WELBIO Department, WEL Research Institute, Wavre, Belgium
- 700 1_
- $a Jaeken, Jaak $u Department of Pediatrics, Center for Metabolic Diseases, University Hospitals Leuven, Leuven, Belgium
- 700 1_
- $a Cantagrel, Vincent $u Developmental Brain Disorders Laboratory, Université Paris Cité, INSERM UMR1163, Imagine Institute, Paris, France
- 700 1_
- $a Van Schaftingen, Emile $u Metabolic Research Group, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; WELBIO Department, WEL Research Institute, Wavre, Belgium. Electronic address: emile.vanschaftingen@uclouvain.be
- 700 1_
- $a Matthijs, Gert $u Laboratory for Molecular Diagnosis, Center for Human Genetics, KU Leuven, Leuven, Belgium. Electronic address: gert.matthijs@kuleuven.be
- 700 1_
- $a Foulquier, François $u Univ. Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France. Electronic address: francois.foulquier@univ-lille.fr
- 700 1_
- $a Bommer, Guido T $u Metabolic Research Group, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; WELBIO Department, WEL Research Institute, Wavre, Belgium. Electronic address: guido.bommer@uclouvain.be
- 773 0_
- $w MED00009444 $t Cell $x 1097-4172 $g Roč. 187, č. 14 (2024), s. 3585-3601.e22
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/38821050 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y - $z 0
- 990 __
- $a 20241015 $b ABA008
- 991 __
- $a 20241024111003 $b ABA008
- 999 __
- $a ok $b bmc $g 2202156 $s 1231735
- BAS __
- $a 3
- BAS __
- $a PreBMC-MEDLINE
- BMC __
- $a 2024 $b 187 $c 14 $d 3585-3601.e22 $e 20240530 $i 1097-4172 $m Cell $n Cell $x MED00009444
- LZP __
- $a Pubmed-20241015
